@article{steele_tosini_siopes_underwood_2006, title={Time keeping by the quail's eye: Cireadian regulation of melatonin production}, volume={145}, ISSN={["1095-6840"]}, DOI={10.1016/j.ygcen.2005.09.004}, abstractNote={Previous studies have shown that eye removal disrupts the circadian body temperature and activity rhythms of Japanese quail supporting the hypothesis that the eyes act as pacemakers within the quail circadian system. Furthermore, the putative ocular pacemakers are coupled to the rest of the circadian system via neural and hormonal outputs. Although the neural pathway has yet to be identified, experiments suggest that the daily rhythm of ocular melatonin synthesis and release is the hormonal output. We sought to strengthen the hypothesis that the eyes are the loci of circadian pacemakers, and that melatonin output is involved, by examining melatonin secretion in cultured quail retinas. Using an in vitro flow-through system we demonstrated that (1) isolated retinal tissue could exhibit a rhythm of melatonin release, (2) the rhythm of melatonin synthesis is directly entrainable by 24-h light–dark cycles, and (3) supplementation of the culture medium with serotonin is necessary for robust, rhythmic production of melatonin in constant darkness. These results show definitively that the eyes are the loci of a biological clock and, in light of previous studies showing the disruptive effects of blinding on the circadian system, strengthen the hypothesis that the ocular clock is a circadian pacemaker that can affect the rest of the circadian system via the cyclic synthesis and release of melatonin. The quail retina is proving to be a valuable in vitro model for investigating properties of circadian pacemakers.}, number={3}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Steele, CT and Tosini, G and Siopes, T and Underwood, H}, year={2006}, month={Feb}, pages={232–236} }
 @article{steele_zivkovic_siopes_underwood_2003, title={Ocular clocks are tightly coupled and act as pacemakers in the circadian system of Japanese quail}, volume={284}, ISSN={["0363-6119"]}, DOI={10.1152/ajpregu.00447.2002}, abstractNote={Our previous studies showed that the eyes of Japanese quail contain a biological clock that drives a daily rhythm of melatonin synthesis. Furthermore, we hypothesized that these ocular clocks are pacemakers because eye removal abolishes freerunning rhythms in constant darkness (DD). If the eyes are indeed acting as pacemakers, we predicted that the two ocular pacemakers in an individual bird must remain in phase in DD and, furthermore, the two ocular pacemakers would rapidly regain coupling after being forced out of phase. These predictions were confirmed by demonstrating that 1) the ocular melatonin rhythms of the two eyes maintained phase for at least 57 days in DD and 2) after ocular pacemakers were forced out of phase by alternately patching the eyes in constant light, two components of body temperature were observed that fused into a consolidated rhythm after 5–6 days in DD, showing pacemaker recoupling. The ability to maintain phase in DD and rapidly recouple after out-of-phase entrainment demonstrates that the eyes are strongly coupled pacemakers that work in synchrony to drive circadian rhythmicity in Japanese quail.}, number={1}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY}, author={Steele, CT and Zivkovic, BD and Siopes, T and Underwood, H}, year={2003}, month={Jan}, pages={R208–R218} }
 @article{moore_siopes_steele_underwood_2002, title={Pineal melatonin secretion, but not ocular melatonin secretion, is sufficient to maintain normal immune responses in Japanese quail (Coturnix coturnix japonica)}, volume={126}, ISSN={["0016-6480"]}, DOI={10.1016/S0016-6480(02)00011-4}, abstractNote={Reports that plasma melatonin is an important immune regulator in avian species have been rather sparse and contradictory. Also, the primary source of immune-modulating melatonin has yet to be determined in birds. In Japanese quail (Coturnix coturnix japonica), the pineal gland and eyes contribute roughly two thirds and one third of the melatonin found in the blood, respectively. Two experiments were conducted to evaluate melatonin as an immune modulator in Japanese quail and to determine the primary source of immune-modulating melatonin in this species. Experiment 1 was designed to evaluate the involvement of the pineal gland and the eyes in immunocompetence. Each of three groups of quail was assigned a surgical treatment and the cellular and humoral immune responses were determined 8 weeks following surgery. The surgical treatments were pinealectomy (Px), sham pinealectomy (SH-Px), and ocular enucleation (eye removal (Ex)). Experiment 2 utilized exogenous melatonin as a replacement to reconstitute immune responses in surgically immunocompromised birds. In this experiment, 50.0 microg/ml of melatonin, or diluent only, was provided to Px and SH-Px birds in the drinking water ad libitum. The cellular and humoral immune responses were determined after 8 weeks of melatonin treatment. In both experiments, a cutaneous basophil hypersensitivity reaction to phytohemagglutinin was measured to evaluate the cellular immune response. To evaluate the humoral immune response, primary antibody titers were determined 7 days postintravenous injection with a Chukar red blood cell suspension. Flow cytometric analysis of peripheral blood lymphocytes was performed to determine the relative percentage of CD4(+) and CD8(+) T- and B-lymphocytes in all treatments of Experiment 2. In Experiment 1, both the SH-Px and Ex surgical treatments produced similar cellular and humoral immune responses, and these responses were significantly greater than those in Px-treated birds. Pinealectomy significantly reduced the cellular and humoral immune responses from SH-Px by 25.8% and 41.3%, respectively. In Experiment 2, Px again resulted in depressed cellular and humoral immune responses. In addition, Px significantly reduced CD8(+) T-lymphocyte numbers compared to SH-Px, while B-lymphocytes remained unchanged. Melatonin administration to Px birds increased the cellular (32.9%) and humoral (30.6%) immune responses to the level of control (SH-Px) birds, although this reconstitution was not due to increased CD8(+) T- or B-lymphocytes. From these data, it was clear that removal of the pineal gland, but not the eyes, reduced cellular and humoral immune responses, which were reconstituted to normal levels by exogenous melatonin. These data suggest that immunodepression is only observed in birds with two thirds of the plasma melatonin removed by pinealectomy. Removal of one third of the plasma melatonin (by ocular enucleation) is not sufficient to reduce cellular and humoral responses in the Japanese quail.}, number={3}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Moore, CB and Siopes, TD and Steele, CT and Underwood, H}, year={2002}, month={May}, pages={352–358} }
 @article{underwood_steele_zivkovic_2001, title={Circadian organization and the role of the pineal in birds}, volume={53}, ISSN={["1097-0029"]}, DOI={10.1002/jemt.1068}, abstractNote={Abstract}, number={1}, journal={MICROSCOPY RESEARCH AND TECHNIQUE}, author={Underwood, H and Steele, CT and Zivkovic, B}, year={2001}, month={Apr}, pages={48–62} }
 @article{underwood_steele_zivkovic_1999, title={Effects of fasting on the circadian body temperature rhythm of Japanese quail}, volume={66}, ISSN={["0031-9384"]}, DOI={10.1016/S0031-9384(98)00287-X}, abstractNote={The effect of food deprivation on the body temperature and activity rhythms of quail was assessed in birds exposed to both light–dark (LD) cycles and to continuous darkness (DD). Quail normally exhibit a daily rhythm of body temperature in LD that will persist in DD (that is, the rhythm is circadian). In LD, 3 days’ food deprivation caused the body temperature to drop below its normal nighttime levels, whereas daytime body temperature was unaffected. In DD, food deprivation caused the body temperature to drop below normal at all phases of the circadian rhythm of body temperature. Accordingly, the lack of hypothermia during the light phase of the LD cycle following food deprivation must represent a direct exogenous or “masking” effect of light, and is not an endogenous property of the circadian system. Blind birds exposed to LD 12:12 exhibited an entrained body temperature rhythm, and food deprivation caused a drop in body temperature below normal levels during both the light and dark phases of the LD cycle. Accordingly, the masking effects of light observed in normal birds on LD cycles is mediated via retinal photoreceptors and not via extraretinal photoreceptors. Measurements of activity levels before and during fasting indicate that fasting-induced hypothermia cannot be explained simply as a consequence of decreases in activity levels. Food deprivation was also observed to cause significant phase shifts in the endogenous rhythm of body temperature.}, number={1}, journal={PHYSIOLOGY & BEHAVIOR}, author={Underwood, H and Steele, CT and Zivkovic, B}, year={1999}, month={Mar}, pages={137–143} }
 @article{zivkovic_underwood_steele_edmonds_1999, title={Formal properties of the circadian and photoperiodic systems of Japanese quail: Phase response curve and effects of T-cycles}, volume={14}, ISSN={["0748-7304"]}, DOI={10.1177/074873099129000786}, abstractNote={ A role for the circadian system in photoperiodic time measurement in Japanese quail is controversial. The authors undertook studies of the circadian and photoperiodic system of Japanese quail to try to identify a role for the circadian system in photoperiodic time measurement. The circadian studies showed that the circadian system acts like a low-amplitude oscillator: It is readily reset by light without significant transients, has a Type 0 phase response curve (PRC), and has a large range of entrainment. In fact, a cycle length that is often used in resonance protocols (LD 6:30) is within the range of entrainment. The authors employed T-cycle experiments; that is, LD cycles with 6-and 14-h photoperiods and period lengths ranging from 18 to 36 h to test for circadian involvement in photoperiodic time measurement. The results did not give evidence for circadian involvement in photoperiodic time measurement: T-cycles utilizing 6-h photoperiods were uniformly noninductive (that is, did not stimulate the reproductive system), whereas T-cycles utilizing 14-h photoperiods were inductive (stimulatory). A good match was observed between the phase-angles exhibited on the T-cycles employing 6-h photoperiods and the predicted phase-angles calculated from a PRC generated from 6-h light pulses. }, number={5}, journal={JOURNAL OF BIOLOGICAL RHYTHMS}, author={Zivkovic, BD and Underwood, H and Steele, CT and Edmonds, K}, year={1999}, month={Oct}, pages={378–390} }