Abstract
Most organisms live in a rhythmic world, where daily environmental variation has a profound effect on their behavior and physiology. In addition to abiotic influence, interactions with other organisms that have their own particular cycles are also part of circadian rhythm formation. In this chapter, we present aspects of the biology of mosquito vectors, more precisely Aedes aegypti, which is a vector of arboviruses of great epidemiological importance, like dengue, Zika, and chikungunya. The successful transmission of the virus depends on the coordination of several behavioral and physiological traits involved in the virus-vector-host interaction. Thus, understanding the mechanisms of endogenous control of rhythmic traits of the mosquito vector and the impact that both environmental variation and virus infection can have on this regulation is key for a reliable estimate of the vectorial capacity. We discuss the infection-driven changes in traits used to calculate parameters of the vectorial capacity, and finally, we review the current knowledge on the molecular mechanisms underlying vector rhythmic behavior and the potential cellular targets of arbovirus infection.
Keywords
- Aedes aegypti
- arbovirus
- behavior
- vectorial capacity
- physiology
- neurotropism
- Zika
- dengue
- chikungunya
- circadian clocks
1. Introduction
1.1 The Aedes aegypti mosquito as a vector of arboviruses
Since they spend most of their life cycle in water, mosquitoes are considered to be primarily aquatic; they gain the terrestrial environment only in adulthood, when they fly in order to seek for food and mates [3, 4, 5]. Easy to distinguish for taxonomists,
The mosquito
Both vector competence and vectorial capacity are critical for arbovirus transmission. Vector competence is the intrinsic ability of a vector to acquire, maintain, and transmit a pathogen to another host. In mosquitoes, a species is considered vector competent when females transmit the pathogen from one vertebrate to another during blood feeding [21]. This competence is related to intrinsic features of the vector, as well as the pathogen, such as pathogen genotype, pathogen strain, and vector strain. Specifically, for the viruses DENV and CHIKV, vector competence has been tested and confirmed in
Although the number of studies on
Other factors may be involved in the vector competence, for example, two different insecticide resistance mechanisms were described to enhance the vector competence of
Vectorial capacity, in turn, is the estimated value through a formula that takes into account a set of parameters of intraspecific physiology and behavior that, associated with environmental conditions, favor natural transmission of a given disease. The vectorial capacity is mainly influenced by population density, biting behavior (frequency of host contact for blood feeding), and mosquito vector survivorship [26]. The concept of vectorial capacity was initially established for the transmission of malaria by vectors of the genus
The World Health Organization emphasizes that mosquito vector control plays an important role in blocking the propagation of critical arboviruses. This is particularly relevant when no vaccines or specific drug treatments are available, as is the case for dengue, Zika, and chikungunya, which have the
2. Aspects of mosquito behavior and their role on the vectorial capacity
In mosquitoes, locomotor activity [31, 32, 33, 34], host-seeking and blood feeding [35], digestion, mate finding and reproduction, and site choice for oviposition [36, 37, 38] are examples of rhythmic patterns that are recognizably modulated by extrinsic factors [39]. While these patterns have been increasingly studied, ecological interactions between hematophagous females and their hosts and pathogens are not well understood [40]. Likewise, how female rhythms affect and are affected by males’ biological aspects associated with courtship and mating is still obscure [41, 42]. An emerging field of study, namely, “the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the pathogens they transmit,” was reviewed in Rund et al. [40].
Cycles in behavior and physiology have coevolved so that the organism’s fitness is optimized. A shift in the rhythm of these traits may disrupt important biological functions leading to impacts on fertility and viability. For instance, in
The vectorial capacity measures the chance of emergence of new cases of the disease departing from one infected human host. As such, the parameters of behavior and physiology used in the calculation assume that mosquitoes are infected. Other parameters include population density, frequency of bites [26, 40], and transmission competency, which are directly influenced by the vector’s behavior and physiology, as well as by the pathogen’s behavior and extrinsic incubation period (EIP) [26, 40, 45].
The magnitudes of most parameters of the vectorial capacity equation are highly dependent on the daily variation of locomotor/flight activity behavior. There are several ways of measuring the pattern of locomotor activity of insect species, varying from the traditional method of reporting the presence of one species in field traps, in different times of the day, to activity monitors and video imaging used in the laboratory. Data generated by all these methods are represented with similar graphics, where the amount of locomotor/flight activity registered at each time interval is plotted on a 24-h graph. Variation in activity is studied according to variation in a
Field and laboratory studies show that
Humans are the main hosts for
Light and temperature are the major environmental factors affecting the rhythmic behavior of most organisms. As such, variation in these factors has a profound effect on the vectorial capacity. For instance, the biting rate of
Mating interaction is another element influencing vectorial capacity. Significant alterations in females’ physiology and behavior happen after copulation, when male accessory gland peptides are transferred along with sperm [50], though contrasting effects have been reported. Augmented host-seeking and blood-feeding activity [31, 51, 52, 53], as well as an increase in oviposition rates [54, 55] and egg development [56], were reported, suggesting that these alterations could boost up the vectorial capacity. On the other hand, Lima-Camara et al. [9] have found a significant decrease in the mean locomotor activity after insemination and after blood feeding in females of
3. The effects of infection on behavior and physiology of mosquito vectors
Since vectorial capacity suffers major influence of vector behavior, studying the degree of modulation that arbovirus exerts on
A consequence of the neurotropic characteristic of these arboviruses is the alteration in the patterns of locomotor activity and feeding behavior. For instance,
Arbovirus infection is also responsible for changes in physiological traits implicated in the estimate of the vectorial capacity. The number of female mosquitoes per host is one of the most important parameters of the vectorial capacity and is directly influenced by life history traits like the number of eggs laid by females (fecundity) and the number of viable offspring (fertility). These traits have been reported altered by arbovirus infection, although the effect varies depending on the virus. Dengue-infected females of
4. Human environmental impact and the effects on vector-host interaction and the risk of disease transmission
Human occupation may lead to profound alterations in the environment, such as global warming and light pollution. Some of these changes impose new selective pressures to all organisms involved with the infection, say pathogens, vectors, and hosts, but also their predators and the vegetation used as nutrition or habitat. The modeling of the effects of global warming on disease transmission indicates a shift in the global distribution of
Altogether, both vectors and hosts undergo behavioral and physiological changes triggered by the virus infection, and in turn, the influence of environmental variation is behind all facets of this interaction. The next section will discuss the endogenous mechanisms regulating rhythmic behavior and physiology, as well as the role of environmental factors on synchronizing these rhythms.
5. Molecular control of the behavior
The different behaviors exhibited by mosquitoes are, in general, driven by internal biological clocks that generate circadian rhythms. These rhythms present a period of nearly, but not exactly, 24 h and are responsible for responses such as host-seeking, breeding site seeking, activity, and rest, among others [67].
These rhythms are directly influenced by natural cues from the environment, and the most important ones are the light/dark and the temperature cycles. These stimuli are received by specific receptors, like photoreceptors (in the eyes and head) and thermoreceptors (along the whole body) and are transmitted to the internal pacemaker or the biological clock itself. Thus, a rhythm or a physiological response is generated from the interaction of the stimuli with the pacemaker neurons [68].
The pacemaker neurons are so-called because they express the clock genes, which are the components of the circadian clock. These genes interact with each other and recruit kinases, phosphatases, and transcription factors to generate oscillating expression in a 24-h cycle [69]. They are also responsible for the regulation of many other genes, the clock-controlled genes (CCGs), that are directly associated with tissue-specific functions [70].
An interesting feature of this clock is its property of environmental synchronization, which adjusts the period to exactly 24 h. One of the most important synchronizers (or
Molecular studies regarding the circadian clock in
In a general manner, the circadian expression pattern of the main clock genes in
5.1 The pacemaker neurons in insects
Clock genes are expressed in specific groups of neurons called pacemaker neurons, in the central nervous system of the organism, and are identified as pacemakers due to PER expression [82]. However, the distribution of these cells in the brain can vary from species to species; while in
In
6. Conclusions
It is known that the virus-host interaction has a crucial importance in the spreading of a pathogen, since mutations in the viral genome or the genetic background of a mosquito population can enhance or even inhibit the replication of the virus in the mosquito. Beyond this genetic interaction, behavior is also directly related to the vectorial capacity of
References
- 1.
Consoli R, Lourenço-de-Oliveira R. Principais Mosquitos de importância sanitária no Brasil. Rio de Janeiro: Fiocruz; 1994. 228 pp - 2.
Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, et al. The global distribution and burden of dengue. Nature. 2013; 496 :504-507. DOI: 10.1038/nature12060 - 3.
Christophers S. Aedes aegypti (L.), the Yellow Fever Mosquito. Its Life History, Bionomics and Structure. Cambridge: The University Press; 1960. 739 pp - 4.
Borror JD, Delong DM. Introdução ao estudo dos insetos. São Paulo: Edgar Blucher; 1988. 653 pp - 5.
Forattini OP. Culicidologia Médica. Vol. 2. São Paulo: Editora da Universidade de São Paulo; 1996. 860 pp - 6.
Rueda LM. Pictorial Keys for the Identification of Mosquitoes (Diptera: Culicidae) Associated with Dengue Virus Transmission. Zootaxa. Vol. 589. Auckland, New Zealand: Magnolia Press; 2004. ISBN 1-877354-46-5 - 7.
Clements AN. The Biology of Mosquitoes: Sensory Reception and Behaviour. London: Chapman and Hall; 1999. 740 pp - 8.
Gentile C, Rivas GB, Meireles-Filho AC, Lima JB, Peixoto AA. Circadian expression of clock genes in two mosquito disease vectors: cry2 is different. Journal of Biological Rhythms. 2009; 24 (6):444-451. DOI: 10.1177/0748730409349169 - 9.
Lima-Camara TN, Lima JB, Bruno RV, Peixoto AA. Effects of insemination and blood-feeding on locomotor activity of Aedes albopictus andAedes aegypti (Diptera: Culicidae) females under laboratory conditions. Parasites & Vectors. 2014;7 (1):304. DOI: 10.1186/1756-3305-7-304 - 10.
Farnesi LC, Barbosa CS, Araripe LO, Bruno RV. The influence of a light and dark cycle on the egg laying activity of Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae). Memórias do Instituto Oswaldo Cruz. 2018;113 :e170362. DOI: 10.1590/0074-02760170362 - 11.
Clements A. The Biology of Mosquitoes: Development, Nutrition and Reproduction. London: Chapman and Hall; 1992. 509 pp - 12.
McMeniman CJ, OʼNeill SL. A virulent Wolbachia infection decreases the viability of the dengue vector Aedes aegypti during periods of embryonic quiescence. PLoS Neglected Tropical Diseases. 2010;4 :e748 - 13.
Boorman JP, Porterfield JS. A simple technique for infection of mosquitoes with viruses; transmission of Zika virus. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1956; 50 (3):238-242 - 14.
Valle D, Pimenta DN, Cunha RV. Dengue: Teorias e Práticas. Rio de Janeiro: Fiocruz; 2015. 458 pp - 15.
Costa-da-Silva AL, Ioshino RS, de Araújo HRC, Kojin BB, de Andrade Zanotto PM, Oliveira DBL, et al. Laboratory strains of Aedes aegypti are competent to brazilian Zika virus. PLoS One. 2017;12 :e0171951 - 16.
Souza-Neto JA, Powell JR, Bonizzoni M. Aedes aegypti vector competence studies: A review. Infection, Genetics and Evolution. 2018;67 :191-209 - 17.
Kliewer JW. Weight and hatchability of Aedes aegypti eggs (Diptera: Culicidae). Annals of the Entomological Society of America. 1961;54 :912-917 - 18.
Rezende GL, Martins AJ, Gentile C, Farnesi LC, Pelajo-Machado M, et al. Embryonic desiccation resistance in Aedes aegypti : Presumptive role of the chitinized serosal cuticle. BMC Developmental Biology. 2008;8 :82. DOI: 10.1186/1471-213X-8-82 - 19.
Farnesi LC, Martins AJ, Valle D, Rezende GL. Embryonic development of Aedes aegypti (Diptera:Culicidae): Influence of different constant temperatures. Memórias do Instituto Oswaldo Cruz. 2009;104 :124-126. DOI: 10.1590/S0074-02762009000100020 - 20.
Farnesi LC, Vargas HCM, Valle D, Rezende GL. Darker eggs of mosquitoes resist more to dry conditions: Melanin enhances serosal cuticle contribution in egg resistance to desiccation in Aedes, Anopheles and Culex vectors. PLoS Neglected Tropical Diseases. 2017; 11 :e0006063. DOI: 10.1371/journal.pntd.0006063 - 21.
WHO. Technical Report Series No. 205. Malaria: Eighth Report of the Expert Committee. Geneva: WHO; 1961 - 22.
Lambrechts L, Paaijmans KP, Fansiri T, Carrington LB, Kramer LD, Thomas MB, et al. Impact of daily temperature fluctuations on dengue virus transmission by Aedes aegypti . Proceedings of the National Academy of Sciences of the United States of America. 2011;108 (18):7460-7465. DOI: 10.1073/pnas.1101377108 - 23.
Chouin-Carneiro T, Vega-Rua A, Vazeille M, Yebakima A, Girod R, Goindin D, et al. Differential susceptibilities of Aedes aegypti andAedes albopictus from the Americas to Zika virus. PLoS Neglected Tropical Diseases. 2016;10 :e0004543 - 24.
Amraoui F, Ben Ayed W, Madec Y, Faraj C, Himmi O, Btissam A, et al. Potential of Aedes albopictus to cause the emergence of arboviruses in Morocco. PLoS Neglected Tropical Diseases. 2019;13 :e0006997 - 25.
Atyame Célestine M, Haoues A, Laurence M, Vazeille M, Diallo M, Mylène W, et al. Insecticide resistance genes affect Culex quinquefasciatus vector competence for West Nile virus. Proceedings of the Royal Society B. 2019;286 (1894):20182273. DOI: 10.1098/rspb.2018.2273 - 26.
Kramer LD, Ciota AT. Dissecting vectorial capacity for mosquito-borne viruses. Current Opinion in Virology. 2015; 15 :112-118 - 27.
Macdonald G. Epidemiologic models in studies of vector borne diseases. Public Health Reports. 1961; 76 :753-764 - 28.
Garrett-Jones C. The human blood index of malaria vectors in relation to epidemiological assessment. Bulletin of the World Health Organization. 1964; 30 :241-261 - 29.
Smith DL, Dushoff J, McKenzie FE. The risk of a mosquito-borne Infection in a heterogeneous environment. PLoS Biology. 2004; 2 (11):e368 - 30.
McSweegan E, Weaver SC, Lecuit M, Frieman M, Morrison TE, Hrynkow S. The global virus network: Challenging chikungunya. Antiviral Research. 2015; 120 :147-152. DOI: 10.1016/j.antiviral.2015.06.003 - 31.
Taylor B, Jones MD. The circadian rhythm of flight activity in the mosquito Aedes aegypti (L.). The phase-setting effects of light-on and light-off. The Journal of Experimental Biology. 1969;51 (1):59-70 - 32.
Jones MDR, Hill M, Hope AM. The circadian flight activity of the mosquito, Anopheles gambiae: Phase setting by the light regime. The Journal of Experimental Biology. 1967; 47 :503-511 - 33.
Rowland M. Changes in the circadian flight activity of the mosquito Anopheles stephensi associated with insemination, blood-feeding, oviposition and nocturnal light intensity. Physiological Entomology. 1989; 14 :77-84. DOI: 10.1111/j.1365-3032.1989.tb00939.x - 34.
Peterson EL. Phase-resetting a mosquito circadian oscillator. Journal of Comparative Physiology. 1980; 138 (3):201-211. DOI: 10.1007/BF00657038 - 35.
Fritz ML, Walker ED, Yunker AJ, Dworkin I. Daily blood feeding rhythms of laboratory-reared north American Culex pipiens . Journal of Circadian Rhythms. 2014;12 :1. DOI: 10.1186/1740-3391-12-1 - 36.
Sumba LA, Okoth K, Deng AL, Githure J, Knols BGJ, Beier JC, et al. Daily oviposition patterns of the African malaria mosquito Anopheles gambiae Giles (Diptera: Culicidae) on different types of aqueous substrates. Journal of Circadian Rhythms. 2004;2 :6. DOI: 10.1186/1740-3391-2-6 - 37.
Fritz ML, Huang J, Walker ED, Bayoh MN, Vulule J, Miller JR. Ovipositional periodicity of caged Anopheles gambiae individuals. Journal of Circadian Rhythms. 2008;6 :2. DOI: 10.1186/1740-3391-6-2 - 38.
Chadee DD, Ritchie SA. Oviposition behaviour and parity rates of Aedes aegypti collected in sticky traps in Trinidad, West Indies. Acta Tropica. 2010;116 :212-216. DOI: 10.1016/j.actatropica.2010.08.008 - 39.
Eilerts DF, Giessen MV, Bose EA, Broxton K, Vinauger C. Odor-specific daily rhythms in the olfactory sensitivity and behavior of Aedes aegypti mosquitoes. Insects. 2018;9 :147. DOI: 10.3390/insects9040147 - 40.
Rund SSC, O’Donnell AJ, Gentile JE, Reece SE. Daily rhythms in mosquitoes and their consequences for malaria transmission. Insects. 2016; 7 :14. DOI: 10.3390/insects7020014 - 41.
Alfonso-Parra C, Ahmed-Braimah YH, Degner EC, Avila FW, Villarreal SM, Pleiss JA, et al. Mating-induced transcriptome changes in the reproductive tract of female Aedes aegypti . PLoS Neglected Tropical Diseases. 2016;10 (2):e0004451. DOI: 10.1371/journal.pntd.0004451 - 42.
Araripe LO, Bezerra JR, Rivas GBS, Bruno RV. Locomotor activity in males of Aedes aegypti can shift in response to females’ presence. Parasites and Vectors. 2018;11 (1):254. DOI: 10.1186/s13071-018-2635-9 - 43.
Xu K, Di Angelo JR, Hughes ME, Hogenesch JB, Sehgal A. The circadian clock interacts with metabolic physiology to influence reproductive fitness. Cell Metabolism. 2011; 13 :639-654. DOI: 10.1016/j.cmet.2011.05.001 - 44.
Gill S, Le HD, Melkani GC, Panda S. Time-restricted feeding attenuates age-related cardiac decline in Drosophila. Science. 2015; 347 :1265-1269. DOI: 10.1126/science.1256682 - 45.
Maciel-de-Freitas R, Koella JC, Lourenço-de-Oliveira R. Lower survival rate, longevity and fecundity of Aedes aegypti (Diptera: Culicidae) females orally challenged with dengue virus serotype 2. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2011;105 :452-458 - 46.
Knols BG, Meuerink J. Odors influence mosquito behavior. Scientia Medica. 1997; 4 :56-63 - 47.
Rund SSC, Bonar NA, Champion MM, Ghazi JP, Houk CM, et al. Daily rhythms in antennal protein and olfactory sensitivity in the malaria mosquito Anopheles gambiae . Scientific Reports. 2013;3 :2494 - 48.
Bailey SL, Heitkemper MM. Circadian rhythmicity of cortisol and body temperature: Morningness-eveningness effects. Chronobiology International. 2001; 18 :249-261 - 49.
Aragao BH. Mosquitoes and yellow fever virus. Memórias do Instituto Oswaldo Cruz. 1939; 34 :565-581. DOI: 10.1590/S0074-02761939000400007 - 50.
Jones MDR. The programming of circadian flight activity in relation to mating and the gonotrophic cycle in the mosquito Aedes aegypti . Physiological Entomology. 1981;87 :511-521. DOI: 10.1111/j.1365-3032.1981.tb00275.x - 51.
Adlakha V, Pillai MKK. Role of male accessory gland substance in the regulation of blood intake by mosquitoes. Journal of Insect Physiology. 1976; 22 :1441-1442 - 52.
Lee J-J, Klowden MJ. A male accessory gland protein that modulates female mosquito (Diptera: Culicidae) host-seeking behavior. Journal of the American Mosquito Control Association. 1999; 15 :4-7 - 53.
Klowden MJ. The check is in the male: Male mosquitoes affect female physiology and behaviour. Journal of the American Mosquito Control Association. 1999; 15 :213-220 - 54.
Leahy MG, Craig GB. Accessory gland substance as a stimulant for oviposition in Aedes aegypti andAedes albopictus . Mosquito News. 1965;25 :448-452 - 55.
Hiss EA, Fuchs MS. The effect of matrone on oviposition in the mosquito, Aedes aegypti . Journal of Insect Physiology. 1972;18 :2217-2227. DOI: 10.1016/0022-1910(72)90250-8 - 56.
Wallis RC, Lang CA. Egg formation and oviposition in bloodfed Aedes aegypti . Mosquito News. 1956;16 :283-286 - 57.
Gaburro J, Bhatti A, Harper J, Jeanne I, Dearnley M, Green D, et al. Neurotropism and behavioral changes associated with Zika infection in the vector Aedes aegypti . Emerging Microbes and Infections. 2018;7 (1):68. DOI: 10.1038/s41426-018-0069-2 - 58.
Salazar MI, Richardson JH, Sánchez-Vargas I, Olson KE, Beaty BJ. Dengue virus type 2: Replication and tropisms in orally infected Aedes aegypti mosquitoes. BMC Microbiology. 2007;7 :9. DOI: 10.1186/1471-2180-7-9 - 59.
Jackson BT, Brewster CC, Paulson SL. La Crosse virus infection alters blood feeding behavior in Aedes triseriatus and Aedes albopictus (Diptera: Culicidae). Journal of Medical Entomology. 2012; 49 :1424-1429 - 60.
Spengler CM, Czeisler CA, Shea SA. An endogenous circadian rhythm of respiratory control in humans. The Journal of Physiology. 2000; 526 :683-694 - 61.
Lima-Camara TN, Bruno RV, Luz PM, Castro MG, Lourenço-de-Oliveira R, Sorgine MH, et al. Dengue infection increases the locomotor activity of Aedes aegypti females. PLoS One. 2011;6 :e17690. DOI: 10.1371/journal.pone.0017690.t001 - 62.
Padilha KP, Resck ME, Cunha OA, Teles-de-Freitas R, Campos SS, Sorgine MH, et al. Zika infection decreases Aedes aegypti locomotor activity but does not influence egg production or viability. Memórias do Instituto Oswaldo Cruz. 2018;113 (10):e180290 - 63.
Vogels CBF, Fros JJ, Pijlman GP, van Loon JJA, Gort G, Koenraadt CJM. Virus interferes with host-seeking behaviour of mosquito. The Journal of Experimental Biology. 2017; 220 (19):3598-3603. DOI: 10.1242/jeb.164186 - 64.
Carlson CJ, Dougherty ER, Getz W. An ecological assessment of the pandemic threat of Zika virus. PLoS Neglected Tropical Diseases. 2016; 10 :e0004968. DOI: 10.1371/journal.pntd.0004968 - 65.
Ryan SJ, Carlson CJ, Mordecai EA, Johnson LR. Global expansion and redistribution of Aedes-borne virus transmission risk with climate change. PLoS Neglected Tropical Diseases. 2019; 13 (3):e0007213. DOI: 10.1371/journal.pntd.0007213 - 66.
Kernbach ME, Newhouse DJ, Miller JM, Hall RJ, Gibbons J, Oberstaller J, et al. Light pollution increases West Nile virus competence of a ubiquitous passerine reservoir species. Proceedings of the Royal Society B. 2019; 286 :20191051. DOI: 10.1098/rspb.2019.1051 - 67.
Saunders DS. Insect Clocks. 3rd ed. Amsterdam: Elsevier; 2002. 560 pp - 68.
Moore-Ede MC, Sulzman FM, Fuller CA. The Clocks that Time Us. Cambridge: Harvard University Press; 1982 - 69.
Mendoza-Viveros L, Bouchard-Cannon P, Hegazi S, Cheng AH, Pastore S, Cheng HM. Molecular modulators of the circadian clock: Lessons from flies and mice. Cellular and Molecular Life Sciences. 2017; 74 (6):1035-1059. DOI: 10.1007/s00018-016-2378-8 - 70.
Stanewsky R. Clock mechanisms in Drosophila. Cell and Tissue Research. 2002; 309 (1):11-26 - 71.
Hardin PE. Molecular genetic analysis of circadian timekeeping in Drosophila. Advances in Genetics. 2011; 74 :141-173. DOI: 10.1016/B978-0-12-387690-4.00005-2 - 72.
Franco DL, Frenkel L, Ceriani MF. The underlying genetics of Drosophila circadian behaviors. Physiology (Bethesda, Md.). 2018; 33 (1):50-62. DOI: 10.1152/physiol.00020.2017 - 73.
Kadener S, Stoleru D, McDonald M, Nawathean P, Rosbash M. Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component. Genes & Development. 2007; 21 (13):1675-1686 - 74.
Emery P, So WV, Kaneko M, Hall JC, Rosbash M. CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. Cell. 1998; 95 :669-679 - 75.
Stanewsky R, Kaneko M, Emery P, Beretta B, Wager-Smith K, Kay SA, et al. The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell. 1998; 95 :681-692 - 76.
Rivas GBS, Teles-de-Freitas R, Pavan MG, Lima JBP, Peixoto AA, Bruno RV. Effects of light and temperature on daily activity and clock gene expression in two mosquito disease vectors. Journal of Biological Rhythms. 2018; 33 (3):272-288. DOI: 10.1177/0748730418772175 - 77.
Yuan Q , Metterville D, Briscoe AD, Reppert SM. Insect cryptochromes: Gene duplication and loss define diverse ways to construct insect circadian clocks. Molecular Biology and Evolution. 2007; 24 (4):948-955 - 78.
Nangle SN, Rosensweig C, Koike N, Tei H, Takahashi JS, Green CB, et al. Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex. eLife. 2014; 3 :e03674. DOI: 10.7554/eLife.03674 - 79.
Zhu H, Sauman I, Yuan Q , Casselman A, Emery-Le M, Emery P, et al. Cryptochromes define a novel circadian clock mechanism in monarch butterflies that may underlie sun compass navigation. PLoS Biology. 2008; 6 (1):e4. DOI: 10.1371/journal.pbio.0060004 - 80.
Ptitsyn AA, Reyes-Solis G, Saavedra-Rodriguez K, Betz J, Suchman EL, Carlson JO, et al. Rhythms and synchronization patterns in gene expression in the Aedes aegypti mosquito. BMC Genomics. 2011;12 :153. DOI: 10.1186/1471-2164-12-153 - 81.
Chahad-Ehlers S, Arthur LP, Lima ALA, Gesto JSM, Torres FR, Peixoto AA, et al. Expanding the view of clock and cycle gene evolution in Diptera. Insect Molecular Biology. 2017; 26 (3):317-331. DOI: 10.1111/imb.12296 - 82.
Helfrich-Förster C. Organization of endogenous clocks in insects. Biochemical Society Transactions. 2005; 33 (Pt 5):957-961 - 83.
Helfrich-Förster C, Yoshii T, Wülbeck C, Grieshaber E, Rieger D, Bachleitner W, et al. The lateral and dorsal neurons of Drosophila melanogaster : New insights about their morphology and function. Cold Spring Harbor Symposia on Quantitative Biology. 2007;72 :517-525. DOI: 10.1101/sqb.2007.72.063 - 84.
Peng Y, Stoleru D, Levine JD, Hall JC, Rosbash M. Drosophila free-running rhythms require intercellular communication. PLoS Biology. 2003; 1 (1):E13. Epub 2003 Sep 15 - 85.
Chahad-Ehlers S, Gentile C, Lima JB, Peixoto AA, Bruno RV. Analysis of cycle gene expression in Aedes aegypti brains by in situ hybridization. PLoS One. 2013;8 (1):e52559. DOI: 10.1371/journal.pone.0052559