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    <source-id>D012380</source-id>
    <source>MESH</source>
    <name>role</name>
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    <source-id>D056631</source-id>
    <source>MESH</source>
    <name>colony collapse</name>
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    <name>abnormal</name>
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    <title>Abnormal, Role change within caste</title>
    <short-name>Abnormal, Role change within caste</short-name>
    <biological-organization-level>Population</biological-organization-level>
    <description>&lt;p&gt;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. &lt;em&gt;Science of the Total Environment&lt;/em&gt; 584-585, 751-775:&lt;/p&gt;

&lt;p&gt;&amp;quot;Like most eusocial insects, honey bees exhibit age-based division of&lt;br /&gt;
labor and progress from nurse to forager as they age (Seeley, 1982).&lt;br /&gt;
This type of age-related behavioral change termed age polyethism, is a&lt;br /&gt;
genomically, nutritionally, and hormonally controlled process (Ament&lt;br /&gt;
et al., 2010; Cheng et al., 2015). Such behavior changes in adult worker&lt;br /&gt;
bees occur in a predictable sequence as theymove fromcentrally located&lt;br /&gt;
in-hive activities including cleaning brood cells (0&amp;ndash;5 d old), to feeding&lt;br /&gt;
brood, capping brood, trimming cappings, and attending the queen&lt;br /&gt;
(2&amp;ndash;11 d old), to peripherally located in-hive activities, such as grooming&lt;br /&gt;
nest-mates, feeding nest-mates, ventilating the hive, producing wax&lt;br /&gt;
and shaping comb cells, receiving and storing nectar, packing pollen,&lt;br /&gt;
and processing nectar into honey and pollen into bee bread (11&amp;ndash;20 d&lt;br /&gt;
old), to outside activities, including guarding the hive and foraging&lt;br /&gt;
(20+ d old) (Seeley, 1982). However, honey bees exhibit phenotypic&lt;br /&gt;
plasticity whereby the rate of behavioral change is highly flexible,&lt;br /&gt;
meaning that under different scenarios, based on colony needs, bees&lt;br /&gt;
will accelerate or reverse their behavioral development. For example,&lt;br /&gt;
to compensate for a loss of foragers, disease, or nutritional stress, bees&lt;br /&gt;
will initiate precocious (early behavioral development) foraging&lt;br /&gt;
(Cheng et al., 2015; Huang and Robinson, 1996). It is biologically plausible&lt;br /&gt;
that early initiation of foraging could lead to a shortage of hive bees&lt;br /&gt;
needed to tend to the brood, which could hinder development of the&lt;br /&gt;
brood. In addition, precocious foraging is correlated with shorter&lt;br /&gt;
lifespans. Therefore, bees that forage earlier tend to do so at the expense&lt;br /&gt;
of their longevity which could impact overall colony resource acquisition&lt;br /&gt;
and productivity (Woyciechowski and Moroń, 2009). However,&lt;br /&gt;
the relationship may be complex given that with seasonal variation,&lt;br /&gt;
food availability, predation pressures, and adverse weather conditions&lt;br /&gt;
that promote greater in-hive activity, older foragers can reverse their&lt;br /&gt;
behavior, regenerate hypopharyngeal glands, and assume roles within&lt;br /&gt;
the hive (Huang and Robinson, 1996).&lt;br /&gt;
Behavioral plasticity is driven, in part, by juvenile hormone (JH) and&lt;br /&gt;
its interplay with Vtg, acting together in a feed-back loop to control the&lt;br /&gt;
onset of labor tasks, such as foraging (Page et al., 2012). For example,&lt;br /&gt;
high Vtg levels suppress JH, delaying onset of foraging behavior,whereas&lt;br /&gt;
high JH suppresses Vtg, causing a decrease in nursing behavior (Page&lt;br /&gt;
et al., 2012). Studies exploring drivers of precocious foraging, using both&lt;br /&gt;
treatment with a JH analog and social manipulation of a single-cohort&lt;br /&gt;
colony of 1 d old bees in the absence of older foragers, induced precocious&lt;br /&gt;
foraging, demonstrating that both hormonal and social interactions&lt;br /&gt;
play a role (Chang et al., 2015; Perry et al., 2015). Active foragers&lt;br /&gt;
produce a pheromone, ethyl oleate, which is transferred to the hive&lt;br /&gt;
bees during trophallaxis or oral food exchange, delaying the rate at&lt;br /&gt;
which bees transition to foraging. Therefore, if the number of foragers&lt;br /&gt;
diminishes, recruitment to foraging can be accelerated. Additionally,&lt;br /&gt;
allatectomy (removal of the corpora allata glands that produce JH) led&lt;br /&gt;
to the discovery that JH is involved in modulating the speed at which&lt;br /&gt;
bees develop into foragers, but not in activation of foraging itself&lt;br /&gt;
(Sullivan et al., 2003). However, studies using ribonucleic acid&lt;/p&gt;

&lt;p&gt;interference (RNAi) to knockdown Vtg production have found the protein&lt;br /&gt;
to have a prominent role in the initiation of honey bee foraging,&lt;br /&gt;
causing an increase in JH titer and extreme precocious foraging (3 d&lt;br /&gt;
old bees) (Guidugli et al., 2005; Marco Antonio et al., 2008).&lt;br /&gt;
Vitellogenin is synthesized in fat body cells, released to the hemolymph&lt;br /&gt;
(circulation), and taken up in developing oocytes (Corona et al.,&lt;br /&gt;
2007). Mature honey bee queens, which lay ~1000 eggs/day, continuously&lt;br /&gt;
synthesize Vtg at high levels, including during periods when egg&lt;br /&gt;
laying ceases (Seehuus et al., 2006; Corona et al., 2007). However, in&lt;br /&gt;
sterile worker bees, Vtg levels have been shown to change throughout&lt;br /&gt;
their lives, with the highest levels observed in the long-lived winter&lt;br /&gt;
bees and lowest in the short-lived summer foragers (M&amp;uuml;nch et al.,&lt;br /&gt;
2015). In addition to the role Vtg plays as an egg yolk protein, it has a&lt;br /&gt;
role in oxidative stress resistance (Corona et al., 2007; Seehuus et al.,&lt;br /&gt;
2006; Amdam et al., 2004).&amp;quot;&lt;/p&gt;
</description>
    <measurement-methodology>&lt;p&gt;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. &lt;em&gt;Science of the Total Environment&lt;/em&gt; 584-585, 751-775:&lt;/p&gt;

&lt;p&gt;&amp;quot;&amp;bull; Age of first forage&lt;br /&gt;
&amp;bull; Hypopharyngeal gland development in forage bees that revert to hive bees&amp;quot;&lt;/p&gt;
</measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <biological-events>
      <biological-event process-id="8727e1dd-a8f2-4fc3-abb5-42c0db85e859" action-id="97f166e9-c4f9-4210-a73e-dbf8f4fcd831"/>
    </biological-events>
    <references>&lt;p&gt;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.&lt;em&gt; &lt;/em&gt;STOTEN. 584-585, 751-775.&lt;/p&gt;

&lt;p&gt;Seeley, T.D., 1982. Adaptive significance of the age polyethism schedule in honeybee colonies.&lt;br /&gt;
Behav. Ecol. Sociobiol. 11 (4), 287&amp;ndash;293.&lt;/p&gt;

&lt;p&gt;Ament, S.A., Wang, Y., Robinson, G.E., 2010. Nutritional regulation of division of labor in&lt;br /&gt;
honey bees: toward a systems biology perspective. Wiley Interdiscip. Rev. Syst. Biol.&lt;br /&gt;
Med. 2 (5), 566&amp;ndash;576.&lt;/p&gt;

&lt;p&gt;Cheng, L.H., Barron, A.B., Cheng, K., 2015. Effects of the juvenile hormone analogue&lt;br /&gt;
methoprene on rate of behavioural development, foraging performance and navigation&lt;br /&gt;
in honey bees (Apis mellifera). J. Exp. Biol. 218, 1715&amp;ndash;1724.&lt;/p&gt;

&lt;p&gt;Huang, Z.Y., Robinson, G.E., 1996. Regulation of honey bee division of labor by colony age&lt;br /&gt;
demography. Behav. Ecol. Sociobiol. 39 (3), 147&amp;ndash;158.&lt;/p&gt;

&lt;p&gt;Woyciechowski, M., Moroń, D., 2009. Life expectancy and onset of foraging in the honeybee&lt;br /&gt;
(Apis mellifera). Insect. Soc. 56 (2), 193&amp;ndash;201.&lt;/p&gt;

&lt;p&gt;Page Jr., R.E., Rueppell, O., Amdam, G.V., 2012. Genetics of reproduction and regulation of&lt;br /&gt;
honeybee (Apis mellifera L.) social behavior. Annu. Rev. Genet. 46, 97&amp;ndash;119.&lt;/p&gt;

&lt;p&gt;Chang, L.H., Barron, A.B., Cheng, K., 2015. Effects of the juvenile hormone analogue&lt;br /&gt;
methoprene on rate of behavioural development, foraging performance and navigation&lt;br /&gt;
in honey bees (Apis mellifera). J. Exp. Biol. 218 (11), 1715&amp;ndash;1724.&lt;/p&gt;

&lt;p&gt;Perry, C., S&amp;oslash;vik, E., Myerscough, M.R., Barron, A.B., 2015. Rapid behavioral maturation accelerates&lt;br /&gt;
failure of stressed honey bee colonies. Proc. Natl. Acad. Sci. U. S. A. 112 (11),&lt;br /&gt;
3427&amp;ndash;3432.&lt;/p&gt;

&lt;p&gt;Sullivan, J.P., Fahrbach, S.E., Harrison, J.F., Capaldi, E.A., Fewell, J.H., Robinson, G.E., 2003.&lt;br /&gt;
Juvenile hormone and division of labor in honey bee colonies: effects of allatectomy&lt;br /&gt;
on flight behavior and metabolism. J. Exp. Biol. 206 (13), 2287&amp;ndash;2296.&lt;/p&gt;

&lt;p&gt;Guidugli, K.R., Nascimento, A.M., Amdam, G.V., Barchuk, A.R., Omholt, S., Sim&amp;otilde;es, Z.L.P.,&lt;br /&gt;
Hartfelder, K., 2005. Vitellogenin regulates hormonal dynamics in the worker caste&lt;br /&gt;
of a eusocial insect. FEBS Lett. 579, 4961&amp;ndash;4965.&lt;/p&gt;

&lt;p&gt;Marco Antonio, D.S., Guidugli-Lazzarini, K.R., do Nascimento, A.M., Sim&amp;otilde;es, Z.L., Harfelder,&lt;br /&gt;
K., 2008. RNAi-mediated silencing of vitellogenin gene function turns honeybee (Apis&lt;br /&gt;
mellifera) workers into extremely precocious foragers. Naturwissenschaften 95 (10),&lt;br /&gt;
953&amp;ndash;961.&lt;/p&gt;

&lt;p&gt;Corona,M., Velarde, R.A., Remolina, S.,Moran-Lauter, A.,Wang, Y., Hughes, K.A., Robinson,&lt;br /&gt;
G.E., 2007. Vitellogenin, juvenile hormone, insulin signaling, and queen honey bee&lt;br /&gt;
longevity. Proc. Natl. Acad. Sci. 104 (17), 7128&amp;ndash;7133.&lt;/p&gt;

&lt;p&gt;Seehuus, S.C., Norberg, K., Gimsa, U., Krekling, T., Amdam, G.V., 2006. Reproductive protein&lt;br /&gt;
protects functionally sterile honey bee workers from oxidative stress. PNAS&lt;br /&gt;
103 (4), 962&amp;ndash;967.&lt;/p&gt;

&lt;p&gt;Amdam, G.V., Sim&amp;otilde;es, Z.L., Hagen, A., Norber, K., Schr&amp;oslash;der, K., Mikkelsen, &amp;Oslash;., Kirkwood,&lt;br /&gt;
T.B., Omholtk, S.W., 2004. Hormonal control of the yolk precursor vitellogenin regulates&lt;br /&gt;
immune function and longevity in honeybees. Exp. Gerontol. 39 (5), 767&amp;ndash;773.&lt;/p&gt;

&lt;p&gt;&amp;nbsp;&lt;/p&gt;
</references>
    <source>AOPWiki</source>
    <creation-timestamp>2016-11-29T18:41:29</creation-timestamp>
    <last-modification-timestamp>2018-06-07T11:21:43</last-modification-timestamp>
  </key-event>
  <key-event id="8763f391-f706-4543-9ae9-b272db963f46">
    <title>Weakened, Colony</title>
    <short-name>Weakened, Colony</short-name>
    <biological-organization-level>Population</biological-organization-level>
    <description>&lt;p&gt;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. &lt;em&gt;Science of the Total Environment&lt;/em&gt; 584-585, 751-775:&lt;/p&gt;

&lt;p&gt;&amp;quot;The characteristics evaluated to determine the strength/health of honey bee colonies, include adequate numbers of adult bees, presence of sealed and open brood, adequate amounts of stored pollen, nectar and sealed honey, the absence of pests and disease, and the presence of a queen that lays eggs in consistent and tight patterns, with limited eggless cells (Sagili and Burgett, 2011). If the colony is weakened by any one (or a combination) of these factors for an extended period, a critical point can be reached&lt;br /&gt;
that will lead to colony failure. Through honey bee population dynamics models, it has been demonstrated that loss of foragers leading to precocious foraging of young bees may restore the overall foraging capacity, but the brood rearing capacity of the colony might be reduced (Khoury et al., 2011). Further, as noted above, precocious foragers are less effective and resilient, causing the forager death rate to increase. The model predicts that sustained forager losses that reduce the force by two-thirds would place a colony at risk for failure (Khoury et al., 2011). Additionally, proper brood rearing is essential to the development of healthy adult bees.&amp;quot;&lt;/p&gt;
</description>
    <measurement-methodology>&lt;p&gt;Text from Table 2 in&amp;nbsp; 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. &lt;em&gt;Science of the Total Environment&lt;/em&gt; 584-585, 751-775:&lt;/p&gt;

&lt;p&gt;&amp;quot;&amp;bull; Count number of adult bees, presence of sealed and open brood, assess amount of food stores by visual method or by weighing,&lt;br /&gt;
assess presence/absence of pests and disease, evaluate egg laying patterns of queen&lt;br /&gt;
&amp;bull; Brood care behavior can be evaluated by filming the brood nest and then recording nursing frequency, total nursing period per&lt;br /&gt;
hour, and average duration of nursing episodes for individual cells&lt;br /&gt;
&amp;bull; Cannibalism of brood can be detected by mapping eggs, larvae and pupae present on brood frames and noting developmental&lt;br /&gt;
stages for each individual, then inspecting daily for missing larvae&lt;br /&gt;
&amp;bull; Assess health of bee: dry weight, muscle development, protein content&amp;quot;&lt;/p&gt;
</measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
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    </biological-events>
    <references>&lt;p&gt;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.&lt;em&gt; &lt;/em&gt;STOTEN. 584-585, 751-775.&lt;/p&gt;

&lt;p&gt;Sagili, R.R., Burgett, D.M., 2011. Evaluating honey bee colonies for pollination: a guide for&lt;br /&gt;
commercial growers and beekeepers. A Pacific Northwest Extension Publication. vol.&lt;br /&gt;
623, pp. 1&amp;ndash;8.&lt;/p&gt;

&lt;p&gt;Khoury, D.S.,Myerscough,M.R., Barron, A.B., 2011. A quantitativemodel of honey bee colony&lt;br /&gt;
population dynamics. PLoS One 6 (4), e18491.&lt;/p&gt;

&lt;p&gt;&amp;nbsp;&lt;/p&gt;
</references>
    <source>AOPWiki</source>
    <creation-timestamp>2016-11-29T18:41:29</creation-timestamp>
    <last-modification-timestamp>2018-06-07T11:04:32</last-modification-timestamp>
  </key-event>
  <key-event id="74c05ae1-b275-4ae7-9126-2f67b62746f1">
    <title>Death/Failure, Colony</title>
    <short-name>Death/Failure, Colony</short-name>
    <biological-organization-level>Population</biological-organization-level>
    <description>&lt;p&gt;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. &lt;em&gt;Science of the Total Environment&lt;/em&gt; 584-585, 751-775:&lt;/p&gt;

&lt;p&gt;&amp;quot;Colony death/failure is defined as demise of a functional colony. Dramatic losses in the number of managed honey bee colonies have been reported across the globe (Potts et al., 2010) and efforts have been undertaken to survey and identify trends in losses over time, particularly in the US and European Union. Most recent survey results collected in the US have shown that managed honey bee colony losses are significantly higher than those deemed acceptable by beekeepers (Seitz et al., 2015). From surveying commercial (&amp;gt;300 colonies), sideline (25&amp;ndash;300 colonies), and small scale &amp;lt;25 colonies) beekeepers, average annual colony losses (both&lt;br /&gt;
summer and winter losses) per operation in the US during 2014&amp;ndash;2015 were 49%, compared to 18.7% that has been identified by beekeepers as an acceptable loss rate (Seitz et al., 2015). Starvation, poor over-winter survival, and weak colonies, were among the most common perceived causes of loss reported by bee keepers (Seitz et al., 2015). Commercial beekeepers, managing thousands of colonies, self-reported colony collapse disorder and pesticides as third and fourth leading reasons for colony loss, respectively (Seitz et al., 2015).&amp;quot;&lt;/p&gt;
</description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
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    </biological-events>
    <references>&lt;p&gt;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.&lt;em&gt; &lt;/em&gt;STOTEN. 584-585, 751-775.&lt;/p&gt;

&lt;p&gt;Potts, S.G., Biesmeijer, J.C., Kremen, C., Neumann, P., Schweiger, O., Kunin, W.E., 2010.&lt;br /&gt;
Global pollinator declines: trends, impacts and drivers. Trends Ecol. Evol. 25 (6),&lt;br /&gt;
345&amp;ndash;353.&lt;/p&gt;

&lt;p&gt;Seitz, N., Traynor, K.S., Steinhauer, N., Rennich, K., Wilson, M.E., Ellis, D., Rose, R., Tarpy,&lt;br /&gt;
D.R., Sagili, R.R., Caron, D.M., Delaplane, K.S., Rangel, J., Lee, K., Baylis, K., Wilkes, J.T.,&lt;br /&gt;
Skinner, J.A., Pettis, J.S., vanEngelsdorp, D., 2015. A national survey of managed&lt;br /&gt;
honey bee 2014&amp;ndash;2015 annual colony losses in the USA. J. Apic. Res. 54 (4), 1&amp;ndash;12.&lt;/p&gt;

&lt;p&gt;&amp;nbsp;&lt;/p&gt;
</references>
    <source>AOPWiki</source>
    <creation-timestamp>2016-11-29T18:41:25</creation-timestamp>
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    <point-of-contact>Allie Always</point-of-contact>
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        <evidence>Not Specified</evidence>
      </relationship>
    </key-event-relationships>
    <applicability>
    </applicability>
    <overall-assessment>
      <description></description>
      <applicability></applicability>
      <key-event-essentiality-summary></key-event-essentiality-summary>
      <weight-of-evidence-summary></weight-of-evidence-summary>
      <known-modulating-factors/>
      <quantitative-considerations></quantitative-considerations>
    </overall-assessment>
    <potential-applications></potential-applications>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2016-11-29T18:41:17</creation-timestamp>
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