This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.jcircadianrhythms.com The latest articles from Journal of Circadian Rhythms (ISSN 1740-3391) published by BioMed Central Background: Light and dark patterns are the major synchronizer of circadian rhythms to the 24-hour solar day. Disruption of circadian rhythms has been associated with a variety of maladies. Ecological studies of human exposures to light are virtually nonexistent, however, making it difficult to determine if, in fact, light-induced circadian disruption directly affects human health. Methods: A newly developed field measurement device recorded circadian light exposures and activity from day-shift and rotating-shift nurses. Circadian disruption defined in terms of behavioral entrainment was quantified for these two groups using phasor analyses of the circular cross-correlations between light exposure and activity. Circadian disruption also was determined for rats subjected to a consistent 12-hour light/12-hour dark pattern (12L:12D) and ones subjected to a "jet-lagged" schedule. Results: Day-shift nurses and rats exposed to the consistent light-dark pattern exhibited pronounced similarities in their circular cross-correlation functions and 24-hour phasor representations except for an approximate 12-hour phase difference between species. The phase difference reflects the diurnal versus nocturnal behavior of humans versus rodents. Phase differences within species likely reflect chronotype differences among individuals. Rotating-shift nurses and rats subjected to the "jet-lagged" schedule exhibited significant reductions in phasor magnitudes compared to the day-shift nurses and the 12L:12D rats. The reductions in the 24-hour phasor magnitudes indicate a loss of behavioral entrainment compared to the nurses and the rats with regular light-dark exposure patterns. Conclusion: This paper provides a quantitative foundation for systematically studying the impact of light-induced circadian disruption in humans and in animal models. Ecological light and activity data are needed to develop the essential insights into circadian entrainment/disruption actually experienced by modern people. These data can now be obtained and analyzed to reveal the interrelationship between actual light exposures and markers of circadian rhythm such as rest-activity patterns, core body temperature, and melatonin synthesis. Moreover, it should now be possible to bridge ecological studies of circadian disruption in humans to parametric studies of the relationships between circadian disruption and health outcomes using animal models. http://www.jcircadianrhythms.com/content/6/1/7 Mark S Rea, Andrew Bierman, Mariana G Figueiro and John D Bullough Journal of Circadian Rhythms 2008, 6:7 2008-05-29 doi:10.1186/1740-3391-6-7 Journal of Circadian Rhythms 1740-3391 6 7 2008-05-29 Background: Delayed sleep phase disorder (DSPD) is a condition in which patients have difficulty falling asleep before the early morning hours and commonly have trouble awakening before late morning or even early afternoon. Several studies have suggested that variations in habitual bedtime are 40–50% heritable. Methods: We recruited a case series of 205 participants, along with 221 controls (DSPD-C) with normal sleep, roughly matched for age, gender, and ancestry. A representative sample of San Diego adults recruited some years before was already available to confirm the control group. Both DSPD and DSPD-C provided blood or saliva samples for DNA and completed extensive questionnaires about sleep habits, sleep history, family history, sleep quality, morningness-eveningness traits, depression, mania, and seasonality of symptoms. The DSPD group wore wrist actigraphs for a median of 13.2 days. The representative sample collected previously had undergone actigraphic recordings, from which 48 hours of data were generally available. Results: The DSPD and DSPD-C samples showed almost no overlap on morningness-eveningness scores. DSPD cases went to bed and arose about 3 hours later than the DSPD-C and the representative sample. DSPD cases reported more difficulties with sleep, poorer sleep quality, and more depression, but there was no significant difference in a history of mania. DSPD cases reported more family history of late bedtimes, but female DSPD reported that their fathers' bedtimes were later than the fathers of male DSPD. Conclusion: These results indicate a DSPD phenotype is familial and associated with unipolar depression. http://www.jcircadianrhythms.com/content/6/1/6 Daniel F Kripke, Katharine M Rex, Sonia Ancoli-Israel, Caroline M Nievergelt, Walt Klimecki and John R Kelsoe Journal of Circadian Rhythms 2008, 6:6 2008-04-29 doi:10.1186/1740-3391-6-6 Journal of Circadian Rhythms 1740-3391 6 6 2008-04-29 Background: Circadian organisation of behavioural and physiological rhythms in mammals is largely driven by the clock in the suprachiasmatic nuclei (SCN) of the hypothalamus. In this clock, a molecular transcriptional repression and activation mechanism generates near 24 hour rhythms. One of the outputs of the molecular clock in specific SCN neurons is arginine-vasopressin (AVP), which is responsive to transcriptional activation by clock gene products. As negative regulators, the protein products of the period genes are thought to repress transcriptional activity of the positive limb after heterodimerisation with CRYPTOCHROME. When both the Per1 and Per2 genes are dysfunctional by targeted deletion of the PAS heterodimer binding domain, mice lose circadian organization of behaviour upon release into constant environmental conditions. To which degree the period genes are involved in the control of AVP output is unknown. Methods: Using an in vitro slice culture setup, SCN-AVP release of cultures made of 10 wildtype and 9 Per1/2 double-mutant mice was assayed. Mice were sacrificed in either the early light phase of the light-dark cycle, or in the early subjective day on the first day of constant dark. Results: Here we report that in arrhythmic homozygous Per1/2 double-mutant mice there is still a diurnal peak in in vitro AVP release from the SCN similar to that of wildtypes but distinctively different from the release pattern from the paraventricular nucleus. Such a modulation of AVP release is unexpected in mice where the circadian clockwork is thought to be disrupted. Conclusion: Our results suggest that the circadian clock in these animals, although deficient in (most) behavioural and molecular rhythms, may still be (partially) functional, possibly as an hourglass mechanism. The level of perturbation of the clock in Per1/2 double mutants may therefore be less than was originally thought. http://www.jcircadianrhythms.com/content/6/1/5 Daan R van der Veen, Ellis GA Mulder, Henrik Oster, Menno P Gerkema and Roelof A Hut Journal of Circadian Rhythms 2008, 6:5 2008-03-20 doi:10.1186/1740-3391-6-5 Journal of Circadian Rhythms 1740-3391 6 5 2008-03-20 Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of PER 2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of PER 2 alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels. http://www.jcircadianrhythms.com/content/6/1/4 Shulin Xiang, Seth B Coffelt, Lulu Mao, Lin Yuan, Qi Cheng and Steven M Hill Journal of Circadian Rhythms 2008, 6:4 2008-03-11 doi:10.1186/1740-3391-6-4 Journal of Circadian Rhythms 1740-3391 6 4 2008-03-11 Background: The plant circadian clock has at its core a feedback loop that includes TIMING OF CAB2 EXPRESSION 1 (TOC1). This protein has an as of yet unknown biochemical activity. It has been noted that the extreme amino-terminus of this protein is distantly related in sequence to response regulators (RR), and thus TOC1 is a member of the so-called pseudo response regulator (PRR) family. As well, the extreme carboxy-terminus has a small sequence stretch related to the other PRRs and CONSTANS (CO)-like proteins, and this peptide stretch has been termed the CCT (for CONSTANS, CONSTANS-LIKE, TOC1) domain. Methods: To extend further our understanding of the TOC1 protein, we performed a ROSETTA structural prediction on TOC1 orthologues from four plant species. Phylogenetic interpretations assisted in model construction. Results: From our models, we suggest that TOC1 is a three-domain protein: TOC1 has an amino-terminal signaling-domain related to response receivers, a carboxy-terminal domain that could participate both in metal binding and in transcriptional regulation, and a linker domain that connects the two. Conclusion: The models we present should prove useful in future hypothesis-driven biochemical analyses to test the predictions that TOC1 is a multi-domain signaling component of the plant circadian clock. http://www.jcircadianrhythms.com/content/6/1/3 Elsebeth Kolmos, Heiko Schoof, Michael Plümer and Seth J Davis Journal of Circadian Rhythms 2008, 6:3 2008-02-25 doi:10.1186/1740-3391-6-3 Journal of Circadian Rhythms 1740-3391 6 3 2008-02-25 Background: Anopheles gambiae s.s. Giles is a major malaria vector in Sub-Saharan Africa. Studies of the basic biology of this mosquito, including oviposition, provide a background for assessing which attributes might be exploited for suppressing A. gambiae populations. Here, we report on when during the diel cycle A. gambiae individuals deposit eggs as compared to the ovipositional patterns of groups. Methods: Battery-powered wall clocks were modified so as to present a unique section of dark and wet ovipositional substrate at hourly intervals over two consecutive 12 h periods. Ovipositional periodicity of mosquito groups (Kisumu laboratory strain or feral females) and individuals was determined by counting the number of eggs present on each section of the ovipositional substrate. Capacity for mid-afternoon oviposition by groups of Kisumu laboratory strain A. gambiae was determined by presenting hypergravid females with an ovipositional substrate exclusively between 1200 and 1600 h. Results: On equatorial time, caged laboratory strain A. gambiae groups deposited 65% of their total eggs between 1800 and 0 h, and the remaining 35% were spread between 0 and 1000 h. Caged house-collected A. gambiae groups deposited 74% of their total eggs between 1800 and 200 h, ceased oviposition for 3 h, and then spread the remaining 26% of their eggs near or after dawn. Ninety-six percent of individual A. gambiae females spread their eggs over a continuous 2–4 h period without interruption. In tests of capacity for mid-afternoon oviposition, females given evening access to an ovipositional resource deposited 2% of their total eggs between 1200 and 1700 h. A. gambiae females given only access to an ovipositional resource between 1200 and 1700 h deposited 3 times more eggs during that time period than did females previously given evening access. Conclusion: Confined individual A. gambiae oviposit in a single ca. 2–4 h continuous bout per 24 h. Oviposition is most probable in early scotophase, mid scotophase, or early photophase. However, some oviposition can occur at any hour during 24 h, especially if females were previously deprived of ovipositional substrate. http://www.jcircadianrhythms.com/content/6/1/2 Megan L Fritz, Juan Huang, Edward D Walker, M Nabie Bayoh, John Vulule and James R Miller Journal of Circadian Rhythms 2008, 6:2 2008-01-25 doi:10.1186/1740-3391-6-2 Journal of Circadian Rhythms 1740-3391 6 2 2008-01-25 The absence of circadian zeitgebers in the social environment causes circadian misalignment, which is often associated with sleep disturbances. Circadian misalignment, defined as a mismatch between the sleep-wake cycle and the timing of the circadian system, can occur either because of inadequate exposure to the light-dark cycle, the most important synchronizer of the circadian system, or reduction in light transmission resulting from ophthalmic diseases (e.g., senile miosis, cataract, diabetic retinopathy, macular degeneration, retinitis pigmentosa, and glaucoma). We propose that glaucoma may be the primary ocular disease that directly compromises photic input to the circadian time-keeping system because of inherent ganglion cell death. Glaucomatous damage to the ganglion cell layer might be particularly harmful to melanopsin. According to histologic and circadian data, a subset of intrinsically photoresponsive retinal ganglion cells, expressing melanopsin and cryptochromes, entrain the endogenous circadian system via transduction of photic input to the thalamus, projecting either to the suprachiasmatic nucleus or the lateral geniculate nucleus. Glaucoma provides a unique opportunity to explore whether in fact light transmission to the circadian system is compromised as a result of ganglion cell loss. http://www.jcircadianrhythms.com/content/6/1/1 Girardin Jean-Louis, Ferdinand Zizi, Douglas R Lazzaro and Arthur H Wolintz Journal of Circadian Rhythms 2008, 6:1 2008-01-10 doi:10.1186/1740-3391-6-1 Journal of Circadian Rhythms 1740-3391 6 1 2008-01-10 Background: Many genes control circadian period in mice. Prior studies suggested a quantitative trait locus (QTL) on proximal mouse chromosome 12 for interstrain differences in circadian period. Since the B6.D2NAhrd/J strain has DBA/2 alleles for a portion of proximal chromosome 12 introgressed onto its C57BL/6J background, we hypothesized that these mice would have a shorter circadian period than C57BL/6J mice. Methods: We compared circadian phenotypes of B6.D2NAhrd/J and C57BL/6 mice: period of general locomotor activity in constant dark and rest/activity pattern in alternating light and dark. We genotyped the B6.D2NAhrd/J mice to characterize the size of the genomic insert. To aid in identifying candidate quantitative trait genes we queried databases about the resident SNPs, whole brain gene expression in C57BL/6J versus DBA/2J mice, and circadian patterns of gene expression. Results: The B6.D2NAhrd/J inbred mice have a shorter circadian period of locomotor activity than the C57BL/6J strain. Furthermore, the genomic insert is associated with another phenotype: the mean phase of activity minimum in the dark part of a light-dark lighting cycle. It was one hour later than in the background strain. The B6.D2NAhrd/J mice have a DBA/2J genomic insert spanning 35.4 to 41.0 megabase pairs on Chromosome 12. The insert contains 15 genes and 12 predicted genes. In this region Ahr (arylhydrocarbon receptor) and Zfp277 (zinc finger protein 277) both contain non-synonymous SNPs. Zfp277 also showed differential expression in whole brain and was cis-regulated. Three genes and one predicted gene showed a circadian pattern of expression in liver, including Zfp277. Conclusion: We not only fine-mapped the QTL for circadian period on chromosome 12 but found a new QTL there as well: an association with the timing of the nocturnal activity-minimum. Candidate quantitative trait genes in this QTL are zinc finger protein 277 and arylhydrocarbon receptor. Arylhydrocarbon receptor is structurally related to Bmal1, a canonical clock gene. http://www.jcircadianrhythms.com/content/5/1/7 John R Hofstetter, Doreen A Svihla-Jones and Aimee R Mayeda Journal of Circadian Rhythms 2007, 5:7 2007-10-31 doi:10.1186/1740-3391-5-7 Journal of Circadian Rhythms 1740-3391 5 7 2007-10-31 Background: An adriamycin-induced impairment of wound healing has been demonstrated experimentally in rats. The purpose of this study is to investigate a possible temporal variation in recovery from the impairment of wound healing caused by adriamycin administration. Methods: The subjects were 120 female Spraque-Dawley rats. They were divided into eight groups, undergoing adriamycin administration (8 mg/kg, i.v.) at 9 a.m. or 9 p.m. on day 0 and laparotomy on day 0, 7, 14 or 21. Blast pressures were recorded after the incision line had been opened, and tissue samples were kept at -30°C for later measurement of hydroxyproline levels. Results: Adriamycin treatment in rats at 9 p.m. resulted in significantly lower blast pressure levels than treatment at 9 a.m. between days 7 and 21, indicating a lag effect of healing time in wounded tissues. However the decreased hydroxyproline levels were not changed at these days and sessions. Conclusion: It is concluded that adriamycin-induced impairment of wound healing in adult female rats exhibits nycthemeral variation. http://www.jcircadianrhythms.com/content/5/1/6 Haluk Alagol, Soykan Dinc, Bilgen Basgut and Nurettin Abacioglu Journal of Circadian Rhythms 2007, 5:6 2007-10-10 doi:10.1186/1740-3391-5-6 Journal of Circadian Rhythms 1740-3391 5 6 2007-10-10 Background: Rapid displacement across multiple time zones results in a conflict between the new cycle of light and dark and the previously entrained program of the internal circadian clock, a phenomenon known as jet lag. In humans, jet lag is often characterized by malaise, appetite loss, fatigue, disturbed sleep and performance deficit, the consequences of which are of particular concern to athletes hoping to perform optimally at an international destination. As a species renowned for its capacity for athletic performance, the consequences of jet lag are also relevant for the horse. However, the duration and severity of jet lag related circadian disruption is presently unknown in this species. We investigated the rates of re-entrainment of serum melatonin and core body temperature (BT) rhythms following an abrupt 6-h phase advance of the LD cycle in the horse. Methods: Six healthy, 2 yr old mares entrained to a 12 h light/12 h dark (LD 12:12) natural photoperiod were housed in a light-proofed barn under a lighting schedule that mimicked the external LD cycle. Following baseline sampling on Day 0, an advance shift of the LD cycle was accomplished by ending the subsequent dark period 6 h early. Blood sampling for serum melatonin analysis and BT readings were taken at 3-h intervals for 24 h on alternate days for 11 days. Disturbances to the subsequent melatonin and BT 24-h rhythms were assessed using repeated measures ANOVA and analysis of Cosine curve fitting parameters. Results: We demonstrate that the equine melatonin rhythm re-entrains rapidly to a 6-h phase advance of an LD12:12 photocycle. The phase shift in melatonin was fully complete on the first day of the new schedule and rhythm phase and waveform were stable thereafter. In comparison, the advance in the BT rhythm was achieved by the third day, however BT rhythm waveform, especially its mesor, was altered for many days following the LD shift. Conclusion: Aside from the temperature rhythm disruption, rapid resynchronization of the melatonin rhythm suggests that the central circadian pacemaker of the horse may possess a particularly robust entrainment response. The consequences for athletic performance remain unknown. http://www.jcircadianrhythms.com/content/5/1/5 Barbara A Murphy, Jeffrey A Elliott, Dawn R Sessions, Mandi M Vick, Erin L Kennedy and Barry P Fitzgerald Journal of Circadian Rhythms 2007, 5:5 2007-08-24 doi:10.1186/1740-3391-5-5 Journal of Circadian Rhythms 1740-3391 5 5 2007-08-24