Circadian expression of the clock gene Per2 is altered in the ruin lizard (Podarcis sicula) when temperature changes.

When exposed to the cold, the body temperature of the ruin lizard (Podarcis sicula), an ectothermic vertebrate, comes into equilibrium with that low environmental temperature. During this time, the behavioral output of the circadian clock, locomotor activity, disappears. We tested the activity of the circadian clockwork at low temperature (6 degrees C) by following the expression of one of its essential components, the Period2 (Per2) gene. Here we show that lizard Per2 (lPer2) expression, which is rhythmic and paralleling the behavioral rhythm of locomotor activity at higher temperature (29 degrees C), becomes constantly high at low temperature. When lizards are re-exposed to high temperature, rhythmic lPer2 expression is re-established after 2 days of adaptation and coincides with onset of locomotor activity. The alteration of the lPer2 expression pattern at low temperature indicates that the activity of the molecular feedback loop is modified under these conditions.

Telomerase induces immortalization of human esophageal keratinocytes without p16INK4a inactivation.

Normal human somatic cells have a finite life span and undergo replicative senescence after a limited number of cell divisions. Erosion of telomeric DNA has emerged as a key factor in senescence, which is antagonized during cell immortalization and transformation. To clarify the involvement of telomerase in the immortalization of keratinocytes, catalytic subunit of telomerase (hTERT) expression was restored in normal human esophageal epithelial cells (EPC2). EPC2-hTERT cells overcame senescence and were immortalized without p16INK4a genetic or epigenetic alterations. p16INK4a was expressed at moderate levels and remained functional as evidenced by induction with UV treatment and binding to cyclin-dependent kinase 4 and 6. There were no mutations in the p53 gene, and p53 was functionally intact. Importantly, senescence could be activated in the immortalized EPC2-hTERT cells by overexpression of oncogenic H-ras or p16INK4a. Furthermore, the EPC2-hTERT cells yielded basal cell hyperplasia in an innovative organotypic culture system in contrast to a normal epithelium from parental cells. These comprehensive results indicate that the expression of telomerase induces immortalization of normal human esophageal keratinocytes without inactivation of p16INK4a/pRb pathway or abrogation of the p53 pathway.

Robust circadian rhythmicity of Per1 and Per2 mutant mice in constant light, and dynamics of Per1 and Per2 gene expression under long and short photoperiods.

The Per1 and Per2 genes are components of the mammalian circadian clock. Mutations in these genes alter phase resetting in response to a nocturnal light pulse, and Per2 mutant mice are known to become arrhythmic in constant darkness. We show that under constant light conditions, Per2 mutant mice exhibit robust activity rhythms as well as body temperature rhythms with a period length that is less than 24 h. In Per1 mutants, the period length of both activity and body temperature rhythms is longer than 24 h in constant light. Per1 mutants prolong their period length (tao) when illuminance is increased, whereas Per2 mutants shorten their endogenous period. Additionally, the authors show that the circadian pattern of Per1 and Per2 gene expression in mice is modified under different photoperiods and that there is a mutual influence of these genes on their timing of expression. We propose that, in mice, the phase relationship between Per1 and Per2 gene expression might be critical for transducing day length information to the organism. Per1 could be part of a morning oscillator tracking dawn, and Per2 could be part of an evening oscillator tracking dusk.