Identification of the mammalian homologues of the Drosophila timeless gene, Timeless1

MRI systems often use magnetic field gradient and shim pulse-shaping networks (pre-emphasis) to correct for magnetic field distortions caused by eddy currents. A pre-emphasis system that uses up to 16 fixed resistor-capacitor (RC) time constants per channel with programmable amplitude coefficients is described. The magnetic fields induced by the pre-emphasis RC time constants serve as a set of basis functions for compensating eddy-current fields induced by the gradient set. The resultant time-varying magnetic field gradient accurately reflects the gradient specified by the pulse programmer. Reductions in eddy-current fields are demonstrated for actively shielded and unshielded gradient sets.     

The late elongated hypocotyl mutation of Arabidopsis disrupts circadian rhythms and the photoperiodic control of flowering

The dominant late elongated hypocotyl (lhy) mutation of Arabidopsis disrupted circadian clock regulation of gene expression and leaf movements and caused flowering to occur independently of photoperiod. LHY was shown to encode a MYB DNA-binding protein. In wild-type plants, the LHY mRNA showed a circadian pattern of expression with a peak around dawn but in the mutant was expressed constantly at high levels. Increased LHY expression from a transgene caused the endogenous gene to be expressed at a constant level, suggesting that LHY was part of a feedback circuit that regulated its own expression. Thus, constant expression of LHY disrupts several distinct circadian rhythms in Arabidopsis, and LHY may be closely associated with the central oscillator of the circadian clock.     

Multitissue circadian expression of rat period homolog (rPer2) mRNA is governed by the mammalian circadian clock, the suprachiasmatic nucleus in the brain

The period (per) gene, controlling circadian rhythms in Drosophila, is expressed throughout the body in a circadian manner. A homolog of Drosophila per was isolated from rat and designated as rPer2. The rPER2 protein showed 39 and 95% amino acid identity with mPER1 and mPER2 (mouse homologs of per) proteins, respectively. A robust circadian fluctuation of rPer2 mRNA expression was discovered not only in the suprachiasmatic nucleus (SCN) of the hypothalamus but also in other tissues including eye, brain, heart, lung, spleen, liver, and kidney. Furthermore, the peripheral circadian expression of rPer2 mRNA was abolished in SCN-lesioned rats that showed behavioral arrhythmicity. These findings suggest that the multitissue circadian expression of rPer2 mRNA was governed by the mammalian brain clock SCN and also suggest that the rPer2 gene was involved in the circadian rhythm of locomotor behavior in mammals.     

DAP-2, the Drosophila homolog of transcription factor AP-2

Between 1985 and 1995, fourteen patients affected by spinal meningiomas underwent surgery at our department. All patients were female, 86 per cent of tumors were thoracic, and the rest was cervical. Thoracic meningiomas occurred predominantly in the lower thoracic spine. One patient had multiple spinal meningiomas, while two other patients had concurrent spinal and cranial meningiomas. The cases are studied with respect to their epidemiology, tumor location, clinical presentation, type of surgical procedure, histopathology and outcome.     

Generation and entrainment of circadian rhythms

1. The present brief review examines some of the new developments in the area of circadian rhythm research. 2. The discovery of the mouse clock and m-per genes and their similarity to other clock genes like per and tim has provided new insight into the control of rhythms in vertebrates. In mice, these genes are expressed in the site of the biological clock, the suprachiasmatic nucleus (SCN), and so will now become a focus of research into the generation of rhythmicity. 3. Because SCN cells expressing endogenous rhythms have a periodicity different from 24 h, there must be mechanisms in place to reset the rhythms on a daily basis. This is achieved in mammals by retinal light perception and neural transmission through several discrete pathways to the SCN. 4. The nature of the neurotransmitters involved in this transfer of environmental information to the timing system is controversial and may even very between similar species but, in the rat, there is compelling evidence that a serotonergic pathway is pre-eminent in mediating the effects of light. How the re-setting is achieved at the cellular level is not known.     

Neurobehavioral effects of solvents and circadian rhythms

Two studies on the combined neurobehavioral effects of shiftwork and solvent exposure were performed: two-shift work/mixed solvent exposure and three-shift work/single solvent exposure (acetone). Repeated measurements of exposure, body temperature, well-being, complaints, and performance were taken during each shift and during several shift cycles. The air concentrations of the solvent mixture were clearly below and of acetone were near the occupational exposure limit values. Both the exposure quality and the circadian factor contributed to the stronger adverse effects under the three-shift condition. The results support the view that exposure effects should be studied and evaluated in relation to shift and time.     

The timSL mutant affects a restricted portion of the Drosophila melanogaster circadian cycle

The circadian rhythm genes period (per) and timeless (tim) are central to contemporary studies on Drosophila circadian rhythms. Mutations in these genes give rise to arrhythmic or period-altered phenotypes, and per and tim gene expression is under clock control. per and tim proteins (PER and TIM) also undergo circadian changes in level and phosphorylation state. The authors previously described a period-altering tim mutation, timSL, with allele-specific effects in different per backgrounds. This mutation also affected the TIM phosphorylation profile during the mid-late night. The authors show here that the single amino acid alteration in TIM-SL is indeed responsible for the phenotype, as a timSL transgene recapitulates the original mutant phenotype and shortens the period of perL flies by 3 h. The authors also show that this mutation has comparable effects in a light-dark cycle, as timSL also accelerates the activity offset during the mid-late night of perL flies. Importantly, timSL advances predominantly the mid-late night region of the perL phase response curve, consistent with the notion that this portion of the cycle is governed by unique rate-limiting steps. The authors propose that TIM and PER phosphorylation are normally rate determining during the mid-late night region of the circadian cycle.     

Identification and characterization of CDS2, a mammalian homolog of the Drosophila CDP-diacylglycerol synthase gene

The technique of intracranial microdialysis was used to investigate the effects of aging on the striatal dopaminergic system of the anesthetized Fischer 344 rat. Microdialysis probes were implanted into the striatum of young (2-8 months) and aged (24-28 months) urethane anesthetized rats. Striatal dialysate levels were analyzed for dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and serotonin (5-HT) by high performance liquid chromatography with electrochemical detection. As compared to the young animals, basal extracellular levels of DA and DOPAC were significantly decreased in two groups of aged animals. Stimulation with excess potassium added through the microdialysis probe produced a robust overflow of DA in the young and aged rat striatum, but the evoked overflow of DA was not diminished in the aged rat striatum as compared to young animals. In contrast, d-amphetamine-evoked overflow of DA was again robust in young and aged animals, but was greatly decreased in the aged rat striatum as compared to the signals recorded in the young rats. Taken together with previous reports, these data support the hypothesis that a major change in the regulation of DA release that occurs in aging involves changes in the function of the neuronal uptake of DA, which may be a compensatory property of DA neurons in senescence.     

Modifications of circadian and circannual rhythms with aging

Whereas biological rhythms are now fairly well documented in young healthy adults, reports in elderly are relatively few for obvious reasons, including the difficulty of setting groups matched in age, sociological and professional background, medical history, and not in need of specific medication. Aging may modify one or several parameters characterizing biological rhythms. The modifications are different from one function to the next, and great care should be given not to mistake changes attributable to the aging process with those resulting from physical and physiological impairment caused by passed environmental aggressions and diseases. Nevertheless, the increasing number of subjects reaching the age of 65 or older, thanks to medical progress, makes necessary establishing time-qualified references values in the aged, as this kind of investigation should lead to an improvement of the conditions and quality of life of elderly subjects.     

Cloning of a structural and functional homolog of the circadian clock gene period from the giant silkmoth Antheraea pernyi

The period (per) gene of Drosophila plays an important role in circadian clock function. Interestingly, homologs of per have not been cloned outside of dipteran species. Using a PCR strategy, we now report the cloning of the cDNA of a per homolog from the silkmoth Antheraea pernyi. The cDNA encodes a protein of 849 amino acids, which shows highest identity (39%) with the per protein of Drosophila virilis. Stretches of high identity between moth and fly proteins are in the amino terminus, the PAS region, and the region surrounding the site of the per mutation in Drosophila. Moth per homolog mRNA levels exhibit a prominent circadian variation in adult heads, and per protein antibodies show a pronounced variation of per antigen staining in photoreceptor nuclei. With sequence information derived from moth and flies, per-like cDNA fragments were readily cloned by PCR from other moth species and a third insect order.     

Photic and circadian regulations of melatonin rhythms in fishes

Photic and circadian regulations of melatonin rhythms in the pineal organ and the retina of several teleosts were studied to investigate the regulatory mechanisms of melatonin rhythms in fishes. In the eyecup preparations of the goldfish, Carassius auratus, both time of day and lighting conditions affected melatonin production, with high melatonin production observed only in the dark-treated group incubated during the 'subjective' night. Thus, in the goldfish retina, local photoreceptors and an ocular circadian clock seem to regulate melatonin production, as in the zebrafish retina and in the pineal organ of a number of teleosts, including the goldfish. However, this circadian regulation of melatonin rhythms is not universal among fishes. Although the superfused pineal organ of the masu salmon Oncorhynchus masou secreted melatonin in a rhythmic fashion under light-dark (LD) cycles, the rhythm disappeared under constant darkness (DD), as in the rainbow trout, with a large amount of melatonin released both during the subjective day and the subjective night. These results suggest that all salmonids lack circadian regulation of melatonin rhythms. Furthermore, when ocular melatonin rhythms were compared in two cyprinids, the ugui Tribolodon hakonensis and the oikawa Zacco platypus occupying different ecological niches, ocular melatonin contents exhibited daily variations, with higher values during the dark phase of LD cycles in both species. The rhythmic changes persisted in the ugui under DD, with higher levels at subjective midnight than at subjective midday; however, ocular melatonin levels in the oikawa were consistently high under DD. Thus, the circadian regulation of melatonin rhythms in fishes is influenced not only by phylogeny, but also by the ecological niches of the animals. These results suggest that the physiological functions of melatonin in the circadian and photoperiodic systems differ among fishes.     

Depletion of a Drosophila homolog of yeast Sup35p disrupts spindle assembly, chromosome segregation, and cytokinesis during male meiosis

This paper addresses the effects of availability and anchoring-and-adjustment on people's beliefs and values concerning environmental issues. The first three studies focus on lay people's perceptions of the causes of large scale environmental risks, the second series of three studies deals with how people value environmental goods and how much they are prepared to pay to mitigate environmental risks. In studies 1-3 we investigate the effects of availability and anchoring-and-adjustment on estimating the contribution of various factors to large scale environmental risks. Highly complex risks such as acid rain and global warming tend to be associated with multiple causes, and our results show that estimating the role of these causes is clearly affected by availability and anchoring-and-adjustment. Both have sizeable effects and persist over time. Moreover, corrective procedures only seem to have a limited effect. Availability and anchoring-and-adjustment not only play a role in judging the possible causes of risks; they also play a role in research attempting to assess the public's willingness to pay (WTP) to protect our environment. The outcomes of WTP surveys are often used as a tool to help policy decision making. In the second part of this article we present three studies on this issue. Results provide further evidence of the impact of the two heuristics on the outcomes of WTP research. Implications for research and practice are briefly discussed.     

A Drosophila homolog of bovine smg p25a GDP dissociation inhibitor undergoes a shift in isoelectric point in the developmental mutant quartet

The Drosophila developmental mutation quartet causes late larval lethality and small imaginal discs and, when expressed in the adult female, has a lethal effect on early embryogenesis. These developmental defects are associated with mitotic defects, which include a low mitotic index in larval brains and incomplete separation of chromosomes in mitosis in the early embryo. quartet mutations also have a biochemical effect, i.e., a basic shift in isoelectric point in three proteins. We have purified one of these proteins, raised an antibody to it, and isolated and sequenced its cDNA. At the amino acid level, the sequence shows 68% identity and 81% similarity to bovine smg p25a GDP dissociation inhibitor (GDI), a regulator of ras-like small GTPases of the rab/SEC4/YPT1 subfamily. The correlation between a basic shift in isoelectric point in Drosophila GDI in quartet mutant tissue and the quartet developmental phenotype raises the possibility that a posttranslational modification of GDI is necessary for its function and that GDI function is essential for development.     

The pineal and circadian rhythms of temperature selection and locomotion in lizards

The existence of a circadian rhythm of behavioral temperature selection has been demonstrated in lizards (Podarcis sicula) held on a thermal gradient in constant darkness. This rhythm becomes temporarily abolished during 1 week following parietalectomy and 2-3 weeks following pinealectomy. Parietalectomy does not affect the locomotor rhythm, while pinealectomy invariably lengthens the freerunning period of this rhythm. These results support the contention of separate control systems for the temperature selection rhythm and the locomotor rhythm. As neither rhythm is definitively abolished by parietalectomy and pinealectomy, other pacemaking components exist elsewhere in the circadian system of Podarcis sicula which can control both rhythms.