Rapid down-regulation of mammalian Period genes during behavioral resetting of the circadian clock

The pervasive role of circadian clocks in regulating physiology and behavior is widely recognized. Their adaptive value is their ability to be entrained by environmental cues such that the internal circadian phase is a reliable predictor of solar time. In mammals, both light and nonphotic behavioral cues can entrain the principal oscillator of the hypothalamic suprachiasmatic nuclei (SCN). However, although light can advance or delay the clock during circadian night, behavioral events trigger phase advances during the subjective day, when the clock is insensitive to light. The recent identification of Period (Per) genes in mammals, homologues of dperiod, which encodes a core element of the circadian clockwork in Drosophila, now provides the opportunity to explain circadian timing and entrainment at a molecular level. In mice, expression of mPer1 and mPer2 in the SCN is rhythmic and acutely up-regulated by light. Moreover, the temporal relations between mRNA and protein cycles are consistent with a clock based on a transcriptional/translational feedback loop. Here we describe circadian oscillations of Per1 and Per2 in the SCN of the Syrian hamster, showing that PER1 protein and mRNA cycles again behave in a manner consistent with a negative-feedback oscillator. Furthermore, we demonstrate that nonphotic resetting has the opposite effect to light: acutely down-regulating these genes. Their sensitivity to nonphotic resetting cues supports their proposed role as core elements of the circadian oscillator. Moreover, this study provides an explanation at the molecular level for the contrasting but convergent effects of photic and nonphotic cues on the clock.

Circadian rhythms in Neurospora crassa: Lipid deficiencies restore robust rhythmicity to null frequency and white-collar mutants

The conidiation rhythm in the fungus Neurospora crassa is a model system for investigating the genetics of circadian clocks. Null mutants at the frq (frequency) locus (frq9 and frq10) make no functional frq gene products and are arrhythmic under standard conditions. The white-collar strains (wc-1 and wc-2) are insensitive to most effects of light, and are also arrhythmic. All three genes are proposed to be central components of the circadian oscillator. We have been investigating two mutants, cel (chain-elongation) and chol-1 (choline-requirer), which are defective in lipid synthesis and affect the period and temperature compensation of the rhythm. We have constructed the double mutant strains chol-1 frq9, chol-1 frq10, chol-1 wc-1, chol-1 wc-2, cel frq9, cel frq10, and cel wc-2. We find that these double mutant strains are robustly rhythmic when assayed under lipid-deficient conditions, indicating that free-running rhythmicity does not require the frq, wc-1, or wc-2 gene products. The rhythms in the double mutant strains are similar to the cel and chol-1 parents, except that they are less sensitive to light. This suggests that the frq, wc-1, and wc-2 gene products may be components of a pathway that normally supplies input to a core oscillator to transduce light signals and sustain rhythmicity. This pathway can be bypassed when lipid metabolism is altered.

Genes, peoples, and languages

The genetic history of a group of populations is usually analyzed by reconstructing a tree of their origins. Reliability of the reconstruction depends on the validity of the hypothesis that genetic differentiation of the populations is mostly due to population fissions followed by independent evolution. If necessary, adjustment for major population admixtures can be made. Dating the fissions requires comparisons with paleoanthropological and paleontological dates, which are few and uncertain. A method of absolute genetic dating recently introduced uses mutation rates as molecular clocks; it was applied to human evolution using microsatellites, which have a sufficiently high mutation rate. Results are comparable with those of other methods and agree with a recent expansion of modern humans from Africa. An alternative method of analysis, useful when there is adequate geographic coverage of regions, is the geographic study of frequencies of alleles or haplotypes. As in the case of trees, it is necessary to summarize data from many loci for conclusions to be acceptable. Results must be independent from the loci used. Multivariate analyses like principal components or multidimensional scaling reveal a number of hidden patterns and evaluate their relative importance. Most patterns found in the analysis of human living populations are likely to be consequences of demographic expansions, determined by technological developments affecting food availability, transportation, or military power. During such expansions, both genes and languages are spread to potentially vast areas. In principle, this tends to create a correlation between the respective evolutionary trees. The correlation is usually positive and often remarkably high. It can be decreased or hidden by phenomena of language replacement and also of gene replacement, usually partial, due to gene flow.

A general additive distance with time-reversibility and rate variation among nucleotide sites.

As additivity is a very useful property for a distance measure, a general additive distance is proposed under the stationary time-reversible (SR) model of nucleotide substitution or, more generally, under the stationary, time-reversible, and rate variable (SRV) model, which allows rate variation among nucleotide sites. A method for estimating the mean distance and the sampling variance is developed. In addition, a method is developed for estimating the variance-covariance matrix of distances, which is useful for the statistical test of phylogenies and molecular clocks. Computer simulation shows (i) if the sequences are longer than, say, 1000 bp, the SR method is preferable to simpler methods; (ii) the SR method is robust against deviations from time-reversibility; (iii) when the rate varies among sites, the SRV method is much better than the SR method because the distance is seriously underestimated by the SR method; and (iv) our method for estimating the sampling variance is accurate for sequences longer than 500 bp. Finally, a test is constructed for testing whether DNA evolution follows a general Markovian model.

Genes that control a temperature-compensated ultradian clock in Caenorhabditis elegans.

Substantial progress has been made in understanding the genetic basis of temperature-compensated circadian clocks. Ultradian rhythms, with a period shorter than 24 h, are at least as widespread as circadian rhythms. We have initiated genetic analysis of defecation behavior, which is controlled by an ultradian clock in Caenorhabditis elegans. The defecation motor program is activated every 45 sec, and this rhythm is temperature compensated. We describe mutations in 12 genes that either shorten or lengthen the cycle period. We find that most of these mutations also disrupt temperature compensation, suggesting that this process is an integral part of the clock. These genes open the way for molecular genetic dissection of this ultradian clock.

Mechanical philosophy, horology, and astronomy.

Bound with this (publisher's binding) is a catalog of books published by G. Bell and sons dated 1896.

L' art de conduire et de regler les pendules et les montres, a l'usage de ceux qui n'ont aucune connoissance d'horlogerie /

Mode of access: Internet.

Reports of the United States commissioners to the Paris universal exposition, 1878. Published under direction of the secretary of state by authority of Congress.

Edited by Edward H. Knight. cf. Appleton, Dict. of Amer. biog., under Knight.

Collection of watches loaned to the Metropolitan Museum of Art of the city of New York by Mrs. George A. Hearn.

"The illustrations are from photographs made expressly for this catalogue by Mr. Charles Balliard."

Juliana Horatia Ewing's works.

v.1. Jackanapes; The story of a short life; etc.-- v.2. Daddy Darwin's dovecot; Melchior's dream; and other tales.-- v.3. Old-fashioned fairy tales; Brothers of pity; and other tales of beasts and men.-- v.4. A great emergency; and other tales.-- v.5. Mrs. Overtheway's remembrances.-- v.6. Lob-lie-by-the-fire; The brownies; and other tales.-- v.7. A flat iron for a farthing.-- v.8. Six to sixteen.-- v.9. Jan of the windmill.-- v.10. We and the world.-- v.11. Mary's meadow; Snap-dragons; Dandelion clocks; and other stories.

Cloches & horloges de L'Hotel de Ville et de L'Hospice d'Alençon.

Mode of access: Internet.

The Jewelers' circular.

Description based on: Vol. 64, no. 1 (Feb. 7, 1912); title from cover.

Collection of watches loaned to the Metropolitan museum of art of the city of New York,

"The illustrations are from photographs made expressly for this catalogue by Mr. Charles Balliard."

The novels and stories.

v. 1. The late Mrs. Null.--v. 2. The Squirrel Inn. The Merry Chanter.--v. 3. Rudder Grange.--v. 4. The hundredth man.--v. 5. Ardis Claverden.--v. 6. The great war syndicate. The stories of the three burglars. The knife that killed Po Hancy. Dusky philosophy.--v. 7. The house of Martha.--v. 8. Pomona's travels. Euphemia among the pelican's. The Rudder Grangers in England. Pomona's daughter.--v. 9. The adventures of Captain Horn.--v. 10. Mrs. Cliff's yacht.--v. 11. The great stone of Sardis. The water-devil.--v. 12. The girl at Cobhurst.--v. 13. The casting away of Mrs. Lecks and Mrs. Aleshine. The vizier of the two-horned Alexander.--v. 14. The associate hermits.--v. 15. Stories. [v.]1: The lady or the tiger? The discourager of hesitancy. The transferred ghost. The spectral mortgage. Every man his own letter-writer. Thar same old coon. Our story. Derelict. On the training of parents. A borrowed month. The baker of Barnbury. The watchmaker's wife.--v. 16. Stories. [v.]2: A tale of negative gravity. Asaph. The remarkable page. The Cloverfield's carriage. A story of assisted fate. My bull-calf. As one woman to another. Our fire-screen. My terminal moraine. Plain fishing.--v. 17. Stories. [v.]3: The griffin and the minor canon. Old Pipes and the dryad. The bee-man of Orn. The queen's museum. The clocks of Rondaine. Christmas before last; or, the fruit of the fragile palm. Prince Hassak's march. The battle of the third cousins. The banished king. The philopena. Amos Kilbright: his adscititious experiences. The Christmas shadrach. The bishop's ghost and the printer's baby. The philosophy of relative existences.--v. 18. Stories. [v.]4: The magic egg. "His wife's deceased sister." The widow's cruise. Captain Eli's best ear. Love before breakfast. The staying power of Sir Rohan. A piece of red calico. The Christmas wreck. My well and what came out of it. Mr. Tolman. My unwilling neighbor. Our archery club.--v. 19. Afield and afloat: The Buller-Podington compact. The romance of a mule-car. The governor-general. Old Applejoy's ghost. Struck by a boomerang. The skipper and El Capitan. "Come in, new year." A sailor's knot. The great staircase at Landover Hall. The ghosts in my toewer. The landsman's tale.--v. 20. Kate Bonnet: the romance of a pirate's daughter.--v. 21. John Gayther's garden.--v. 22. The captain's toll-gate.--v. 23. A bicycle of Cathay. With a memorial sketch of Mr. Stockton and a bibliography of his works.