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Event: 1108

Key Event Title

The KE title should describe a discrete biological change that can be measured. It should generally define the biological object or process being measured and whether it is increased, decreased, or otherwise definably altered relative to a control state. For example “enzyme activity, decreased”, “hormone concentration, increased”, or “growth rate, decreased”, where the specific enzyme or hormone being measured is defined. More help

Abnormal, Role change within caste

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. The short name should be less than 80 characters in length. More help
Abnormal, Role change within caste

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. Note, KEs should be defined within a particular level of biological organization. Only KERs should be used to transition from one level of organization to another. Selection of the level of biological organization defines which structured terms will be available to select when defining the Event Components (below). More help

Key Event Components

Further information on Event Components and Biological Context may be viewed on the attached pdf.Because one of the aims of the AOP-KB is to facilitate de facto construction of AOP networks through the use of shared KE and KER elements, authors are also asked to define their KEs using a set of structured ontology terms (Event Components). In the absence of structured terms, the same KE can readily be defined using a number of synonymous titles (read by a computer as character strings). In order to make these synonymous KEs more machine-readable, KEs should also be defined by one or more “event components” consisting of a biological process, object, and action with each term originating from one of 22 biological ontologies (Ives, et al., 2017; See List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signalling by that receptor).Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. More help
Process Object Action
role abnormal

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
nAChR activation - colony loss 7 KeyEvent Arthur Author (send email) Open for comment. Do not cite
nAChR activation - colony loss 5 KeyEvent Cataia Ives (send email) Open for comment. Do not cite
Nosema to role change to colony loss/failure KeyEvent Allie Always (send email) Under Development: Contributions and Comments Welcome


This is a structured field used to identify specific agents (generally chemicals) that can trigger the KE. Stressors identified in this field will be linked to the KE in a machine-readable manner, such that, for example, a stressor search would identify this as an event the stressor can trigger. NOTE: intermediate or downstream KEs in one AOP may function as MIEs in other AOPs, meaning that stressor information may be added to the KE description, even if it is a downstream KE in the pathway currently under development.Information concerning the stressors that may trigger an MIE can be defined using a combination of structured and unstructured (free-text) fields. For example, structured fields may be used to indicate specific chemicals for which there is evidence of an interaction relevant to this MIE. By linking the KE description to a structured chemical name, it will be increasingly possible to link the MIE to other sources of chemical data and information, enhancing searchability and inter-operability among different data-sources and knowledgebases. The free-text section “Evidence for perturbation of this MIE by stressor” can be used both to identify the supporting evidence for specific stressors triggering the MIE as well as to define broad chemical categories or other properties that classify the stressors able to trigger the MIE for which specific structured terms may not exist. More help

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected from an ontology. In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

The structured ontology terms for life-stage are more comprehensive than those for taxa, but may still require further description/development and explanation in the free text section. More help

Sex Applicability

The authors must select from one of the following: Male, female, mixed, asexual, third gender, hermaphrodite, or unspecific. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. For example, the biological state being measured could be the activity of an enzyme, the expression of a gene or abundance of an mRNA transcript, the concentration of a hormone or protein, neuronal activity, heart rate, etc. The biological compartment may be a particular cell type, tissue, organ, fluid (e.g., plasma, cerebrospinal fluid), etc. The role in the biology could describe the reaction that an enzyme catalyses and the role of that reaction within a given metabolic pathway; the protein that a gene or mRNA transcript codes for and the function of that protein; the function of a hormone in a given target tissue, physiological function of an organ, etc. Careful attention should be taken to avoid reference to other KEs, KERs or AOPs. Only describe this KE as a single isolated measurable event/state. This will ensure that the KE is modular and can be used by other AOPs, thereby facilitating construction of AOP networks. More help

Text from LaLone et al. (2017) Weight of evidence evaluation of a network of adverse outcome pathways linking activaiton of the nicotinic acetylcholine receptor in honey bees to colony death. Science of the Total Environment 584-585, 751-775:

"Like most eusocial insects, honey bees exhibit age-based division of labor and progress from nurse to forager as they age (Seeley, 1982). This type of age-related behavioral change termed age polyethism, is a genomically, nutritionally, and hormonally controlled process (Ament et al., 2010; Cheng et al., 2015). Such behavior changes in adult worker bees occur in a predictable sequence as theymove fromcentrally located in-hive activities including cleaning brood cells (0–5 d old), to feeding brood, capping brood, trimming cappings, and attending the queen (2–11 d old), to peripherally located in-hive activities, such as grooming nest-mates, feeding nest-mates, ventilating the hive, producing wax and shaping comb cells, receiving and storing nectar, packing pollen, and processing nectar into honey and pollen into bee bread (11–20 d old), to outside activities, including guarding the hive and foraging (20+ d old) (Seeley, 1982). However, honey bees exhibit phenotypic plasticity whereby the rate of behavioral change is highly flexible, meaning that under different scenarios, based on colony needs, bees will accelerate or reverse their behavioral development. For example, to compensate for a loss of foragers, disease, or nutritional stress, bees will initiate precocious (early behavioral development) foraging (Cheng et al., 2015; Huang and Robinson, 1996). It is biologically plausible that early initiation of foraging could lead to a shortage of hive bees needed to tend to the brood, which could hinder development of the brood. In addition, precocious foraging is correlated with shorter lifespans. Therefore, bees that forage earlier tend to do so at the expense of their longevity which could impact overall colony resource acquisition and productivity (Woyciechowski and Moroń, 2009). However, the relationship may be complex given that with seasonal variation, food availability, predation pressures, and adverse weather conditions that promote greater in-hive activity, older foragers can reverse their behavior, regenerate hypopharyngeal glands, and assume roles within the hive (Huang and Robinson, 1996). Behavioral plasticity is driven, in part, by juvenile hormone (JH) and its interplay with Vtg, acting together in a feed-back loop to control the onset of labor tasks, such as foraging (Page et al., 2012). For example, high Vtg levels suppress JH, delaying onset of foraging behavior,whereas high JH suppresses Vtg, causing a decrease in nursing behavior (Page et al., 2012). Studies exploring drivers of precocious foraging, using both treatment with a JH analog and social manipulation of a single-cohort colony of 1 d old bees in the absence of older foragers, induced precocious foraging, demonstrating that both hormonal and social interactions play a role (Chang et al., 2015; Perry et al., 2015). Active foragers produce a pheromone, ethyl oleate, which is transferred to the hive bees during trophallaxis or oral food exchange, delaying the rate at which bees transition to foraging. Therefore, if the number of foragers diminishes, recruitment to foraging can be accelerated. Additionally, allatectomy (removal of the corpora allata glands that produce JH) led to the discovery that JH is involved in modulating the speed at which bees develop into foragers, but not in activation of foraging itself (Sullivan et al., 2003). However, studies using ribonucleic acid

interference (RNAi) to knockdown Vtg production have found the protein to have a prominent role in the initiation of honey bee foraging, causing an increase in JH titer and extreme precocious foraging (3 d old bees) (Guidugli et al., 2005; Marco Antonio et al., 2008). Vitellogenin is synthesized in fat body cells, released to the hemolymph (circulation), and taken up in developing oocytes (Corona et al., 2007). Mature honey bee queens, which lay ~1000 eggs/day, continuously synthesize Vtg at high levels, including during periods when egg laying ceases (Seehuus et al., 2006; Corona et al., 2007). However, in sterile worker bees, Vtg levels have been shown to change throughout their lives, with the highest levels observed in the long-lived winter bees and lowest in the short-lived summer foragers (Münch et al., 2015). In addition to the role Vtg plays as an egg yolk protein, it has a role in oxidative stress resistance (Corona et al., 2007; Seehuus et al., 2006; Amdam et al., 2004)."

How It Is Measured or Detected

One of the primary considerations in evaluating AOPs is the relevance and reliability of the methods with which the KEs can be measured. The aim of this section of the KE description is not to provide detailed protocols, but rather to capture, in a sentence or two, per method, the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements. Methods that can be used to detect or measure the biological state represented in the KE should be briefly described and/or cited. These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA).Key considerations regarding scientific confidence in the measurement approach include whether the assay is fit for purpose, whether it provides a direct or indirect measure of the biological state in question, whether it is repeatable and reproducible, and the extent to which it is accepted in the scientific and/or regulatory community. Information can be obtained from the OECD Test Guidelines website and the EURL ECVAM Database Service on Alternative Methods to Animal Experimentation (DB-ALM). ?

Text from Table 2 in LaLone et al. (2017) Weight of evidence evaluation of a network of adverse outcome pathways linking activaiton of the nicotinic acetylcholine receptor in honey bees to colony death. Science of the Total Environment 584-585, 751-775:

"• Age of first forage • Hypopharyngeal gland development in forage bees that revert to hive bees"

Domain of Applicability

This free text section should be used to elaborate on the scientific basis for the indicated domains of applicability and the WoE calls (if provided). While structured terms may be selected to define the taxonomic, life stage and sex applicability (see structured applicability terms, above) of the KE, the structured terms may not adequately reflect or capture the overall biological applicability domain (particularly with regard to taxa). Likewise, the structured terms do not provide an explanation or rationale for the selection. The free-text section on evidence for taxonomic, life stage, and sex applicability can be used to elaborate on why the specific structured terms were selected, and provide supporting references and background information.  More help


List of the literature that was cited for this KE description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide ( (OECD, 2015). More help

LaLone, C.A., Villeneuve, D.L., Wu-Smart, J., Milsk, R.Y., Sappington, K., Garber, K.V., Housenger, J. and Ankley, G.T., 2017. Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death. STOTEN. 584-585, 751-775.

Seeley, T.D., 1982. Adaptive significance of the age polyethism schedule in honeybee colonies. Behav. Ecol. Sociobiol. 11 (4), 287–293.

Ament, S.A., Wang, Y., Robinson, G.E., 2010. Nutritional regulation of division of labor in honey bees: toward a systems biology perspective. Wiley Interdiscip. Rev. Syst. Biol. Med. 2 (5), 566–576.

Cheng, L.H., Barron, A.B., Cheng, K., 2015. Effects of the juvenile hormone analogue methoprene on rate of behavioural development, foraging performance and navigation in honey bees (Apis mellifera). J. Exp. Biol. 218, 1715–1724.

Huang, Z.Y., Robinson, G.E., 1996. Regulation of honey bee division of labor by colony age demography. Behav. Ecol. Sociobiol. 39 (3), 147–158.

Woyciechowski, M., Moroń, D., 2009. Life expectancy and onset of foraging in the honeybee (Apis mellifera). Insect. Soc. 56 (2), 193–201.

Page Jr., R.E., Rueppell, O., Amdam, G.V., 2012. Genetics of reproduction and regulation of honeybee (Apis mellifera L.) social behavior. Annu. Rev. Genet. 46, 97–119.

Chang, L.H., Barron, A.B., Cheng, K., 2015. Effects of the juvenile hormone analogue methoprene on rate of behavioural development, foraging performance and navigation in honey bees (Apis mellifera). J. Exp. Biol. 218 (11), 1715–1724.

Perry, C., Søvik, E., Myerscough, M.R., Barron, A.B., 2015. Rapid behavioral maturation accelerates failure of stressed honey bee colonies. Proc. Natl. Acad. Sci. U. S. A. 112 (11), 3427–3432.

Sullivan, J.P., Fahrbach, S.E., Harrison, J.F., Capaldi, E.A., Fewell, J.H., Robinson, G.E., 2003. Juvenile hormone and division of labor in honey bee colonies: effects of allatectomy on flight behavior and metabolism. J. Exp. Biol. 206 (13), 2287–2296.

Guidugli, K.R., Nascimento, A.M., Amdam, G.V., Barchuk, A.R., Omholt, S., Simões, Z.L.P., Hartfelder, K., 2005. Vitellogenin regulates hormonal dynamics in the worker caste of a eusocial insect. FEBS Lett. 579, 4961–4965.

Marco Antonio, D.S., Guidugli-Lazzarini, K.R., do Nascimento, A.M., Simões, Z.L., Harfelder, K., 2008. RNAi-mediated silencing of vitellogenin gene function turns honeybee (Apis mellifera) workers into extremely precocious foragers. Naturwissenschaften 95 (10), 953–961.

Corona,M., Velarde, R.A., Remolina, S.,Moran-Lauter, A.,Wang, Y., Hughes, K.A., Robinson, G.E., 2007. Vitellogenin, juvenile hormone, insulin signaling, and queen honey bee longevity. Proc. Natl. Acad. Sci. 104 (17), 7128–7133.

Seehuus, S.C., Norberg, K., Gimsa, U., Krekling, T., Amdam, G.V., 2006. Reproductive protein protects functionally sterile honey bee workers from oxidative stress. PNAS 103 (4), 962–967.

Amdam, G.V., Simões, Z.L., Hagen, A., Norber, K., Schrøder, K., Mikkelsen, Ø., Kirkwood, T.B., Omholtk, S.W., 2004. Hormonal control of the yolk precursor vitellogenin regulates immune function and longevity in honeybees. Exp. Gerontol. 39 (5), 767–773.