682 research outputs found

    Recruitment Strategies and Colony Size in Ants

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    Ants use a great variety of recruitment methods to forage for food or find new nests, including tandem running, group recruitment and scent trails. It has been known for some time that there is a loose correlation across many taxa between species-specific mature colony size and recruitment method. Very small colonies tend to use solitary foraging; small to medium sized colonies use tandem running or group recruitment whereas larger colonies use pheromone recruitment trails. Until now, explanations for this correlation have focused on the ants' ecology, such as food resource distribution. However, many species have colonies with a single queen and workforces that grow over several orders of magnitude, and little is known about how a colony's organization, including recruitment methods, may change during its growth. After all, recruitment involves interactions between ants, and hence the size of the colony itself may influence which recruitment method is used—even if the ants' behavioural repertoire remains unchanged. Here we show using mathematical models that the observed correlation can also be explained by recognizing that failure rates in recruitment depend differently on colony size in various recruitment strategies. Our models focus on the build up of recruiter numbers inside colonies and are not based on optimality arguments, such as maximizing food yield. We predict that ant colonies of a certain size should use only one recruitment method (and always the same one) rather than a mix of two or more. These results highlight the importance of the organization of recruitment and how it is affected by colony size. Hence these results should also expand our understanding of ant ecology

    A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

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    During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

    The Location and Nature of General Anesthetic Binding Sites on the Active Conformation of Firefly Luciferase; A Time Resolved Photolabeling Study

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    Firefly luciferase is one of the few soluble proteins that is acted upon by a wide variety of general anesthetics and alcohols; they inhibit the ATP–driven production of light. We have used time–resolved photolabeling to locate the binding sites of alcohols during the initial light output, some 200 ms after adding ATP. The photolabel 3-azioctanol inhibited the initial light output with an IC50 of 200 µM, close to its general anesthetic potency. Photoincorporation of [3H]3-azioctanol into luciferase was saturable but weak. It was enhanced 200 ms after adding ATP but was negligible minutes later. Sequencing of tryptic digests by HPLC–MSMS revealed a similar conformation–dependence for photoincorporation of 3-azioctanol into Glu-313, a residue that lines the bottom of a deep cleft (vestibule) whose outer end binds luciferin. An aromatic diazirine analog of benzyl alcohol with broader side chain reactivity reported two sites. First, it photolabeled two residues in the vestibule, Ser-286 and Ile-288, both of which are implicated with Glu-313 in the conformation change accompanying activation. Second, it photolabeled two residues that contact luciferin, Ser-316 and Ser-349. Thus, time resolved photolabeling supports two mechanisms of action. First, an allosteric one, in which anesthetics bind in the vestibule displacing water molecules that are thought to be involved in light output. Second, a competitive one, in which anesthetics bind isosterically with luciferin. This work provides structural evidence that supports the competitive and allosteric actions previously characterized by kinetic studies

    Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome : a systematic review and meta-analysis

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    Aims/hypothesis FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. Results A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10−11) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10−10). This translated into an approximately 3.3 kg/m2 increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. Conclusions/interpretation The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS

    Spatial effects, sampling errors, and task specialization in the honey bee

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    Task allocation patterns should depend on the spatial distribution of work within the nest, variation in task demand, and the movement patterns of workers, however, relatively little research has focused on these topics. This study uses a spatially explicit agent based model to determine whether such factors alone can generate biases in task performance at the individual level in the honey bees, Apis mellifera. Specialization (bias in task performance) is shown to result from strong sampling error due to localized task demand, relatively slow moving workers relative to nest size, and strong spatial variation in task demand. To date, specialization has been primarily interpreted with the response threshold concept, which is focused on intrinsic (typically genotypic) differences between workers. Response threshold variation and sampling error due to spatial effects are not mutually exclusive, however, and this study suggests that both contribute to patterns of task bias at the individual level. While spatial effects are strong enough to explain some documented cases of specialization; they are relatively short term and not explanatory for long term cases of specialization. In general, this study suggests that the spatial layout of tasks and fluctuations in their demand must be explicitly controlled for in studies focused on identifying genotypic specialists

    The potential for land sparing to offset greenhouse gas emissions from agriculture

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    Greenhouse gas emissions from global agriculture are increasing at around 1% per annum, yet substantial cuts in emissions are needed across all sectors. The challenge of reducing agricultural emissions is particularly acute, because the reductions achievable by changing farming practices are limited and are hampered by rapidly rising food demand. Here we assess the technical mitigation potential offered by land sparing-increasing agricultural yields, reducing farm land area and actively restoring natural habitats on the land spared. Restored habitats can sequester carbon and can offset emissions from agriculture. Using the United Kingdom as an example, we estimate net emissions in 2050 under a range of future agricultural scenarios. We find that a land-sparing strategy has the technical potential to achieve significant reductions in net emissions from agriculture and land-use change. Coupling land sparing with demand-side strategies to reduce meat consumption and food waste can further increase the technical mitigation potential, however economic and implementation considerations might limit the degree to which this technical potential could be realised in practice.This research was funded by the Cambridge Conservation Initiative Collaborative Fund for Conservation and we thank its major sponsor Arcadia. We thank J. Bruinsma for the provision of demand data, the CEH for the provision of soil data and J. Spencer for invaluable discussions. A.L. was supported by a Gates Cambridge Scholarship.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nclimate291

    Reaching a Consensus: Terminology and Concepts Used in Coordination and Decision-Making Research

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    Research on coordination and decision-making in humans and nonhuman primates has increased considerably throughout the last decade. However, terminology has been used inconsistently, hampering the broader integration of results from different studies. In this short article, we provide a glossary containing the central terms of coordination and decision-making research. The glossary is based on previous definitions that have been critically revised and annotated by the participants of the symposium “Where next? Coordination and decision-making in primate groups” at the XXIIIth Congress of the International Primatological Society (IPS) in Kyoto, Japan. We discuss a number of conceptual and methodological issues and highlight consequences for their implementation. In summary, we recommend that future studies on coordination and decision-making in animal groups do not use the terms “combined decision” and “democratic/despotic decision-making.” This will avoid ambiguity as well as anthropocentric connotations. Further, we demonstrate the importance of 1) taxon-specific definitions of coordination parameters (initiation, leadership, followership, termination), 2) differentiation between coordination research on individual-level process and group-level outcome, 3) analyses of collective action processes including initiation and termination, and 4) operationalization of successful group movements in the field to collect meaningful and comparable data across different species

    Mesoscopic organization reveals the constraints governing C. elegans nervous system

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    One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations, such as optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis, we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.Comment: Published version, Minor modifications, 16 pages, 9 figure

    Implementation of the Time-to-Event Continuous Reassessment Method Design in a Phase I Platform Trial Testing Novel Radiotherapy-Drug Combinations-CONCORDE

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    \ua9 2022 by American Society of Clinical Oncology. PURPOSE CONCORDE is the first phase I drug-radiotherapy (RT) combination platform in non-small-cell lung cancer, designed to assess multiple different DNA damage response inhibitors in combination with radical thoracic RT. Time-to-event continuous reassessment method (TiTE-CRM) methodology will inform dose escalation individually for each different DNA damage response inhibitor-RT combination and a randomized calibration arm will aid attribution of toxicities. We report in detail the novel statistical design and implementation of the TiTE-CRM in the CONCORDE trial. METHODS Statistical parameters were calibrated following recommendations by Lee and Cheung. Simulations were performed to assess the operating characteristics of the chosen models and were written using modified code from the R package dfcrm. RESULTS The results of the simulation work showed that the proposed statistical model setup can answer the research questions under a wide range of potential scenarios. The proposed models work well under varying levels of recruitment and with multiple adaptations to the original methodology. CONCLUSION The results demonstrate how TiTE-CRM methodology may be used in practice in a complex dose-finding platform study. We propose that this novel phase I design has potential to overcome some of the logistical barriers that for many years have prevented timely development of novel drug-RT combinations

    Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk

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    © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. INTRODUCTION: Lung cancer is the world's leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. METHODS AND ANALYSIS: Using a single-consent Zelen's design, ever-smokers aged 55-80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. ETHICS AND DISSEMINATION: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. TRIAL REGISTRATION NUMBERS: ISRCTN42704678 and NCT03750110
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