Natural Light Exposure,Sleep and Depression among Day Workers and Shiftworkers at Arctic and Equatorial Latitudes

Objectives

This study aimed to investigate the relationship between individual natural light exposure, sleep need, and depression at two latitudes, one extreme with a few hours of light per day during winter, and the other with equal hours of light and darkness throughout the year.

Methods

This cross-sectional study included a sample of Brazilian workers (Equatorial, n = 488 workers) and a Swedish sample (Arctic, n = 1,273).

Results

The reported mean total natural light exposure per 4-week cycle differed significantly between the Equatorial and Arctic regions. However, shiftworkers from both sites reported similar hours of natural light exposure. Short light exposure was a predictor for insufficient sleep.

Conclusion

Reduced exposure to natural light appears to increase the perception of obtaining insufficient sleep. Arctic workers were more prone to develop depression than Equatorial workers.     

Effect of Menopause on Melatonin and Alertness Rhythms Investigated in Constant Routine Conditions

Although studies have reported the effects of the menstrual cycle on melatonin rhythmicity, none has investigated the effects of menopause on the melatonin rhythm. The circadian rhythm in melatonin and its relationship to subjective alertness was investigated in pre‐ and postmenopausal women under constant routine conditions (controlled posture, dim lighting, calorie intake, temperature, and prolonged wakefulness). Eleven healthy pre‐menopausal (42±4 yr) and 10 postmenopausal women (55±2 yr) participated in the study. Salivary melatonin samples and subjective measures of alertness and sleepiness were assessed hourly during the 22 h constant routine protocol. Postmenopausal women had a significantly earlier melatonin acrophase (1.1±0.5 h clock time in decimal h; mean±SEM, p<0.05) compared to the pre‐menopausal women (2.3±0.3 h). There was no significant difference between melatonin onset and amplitude between the pre‐menopausal and postmenopausal women. Self‐rated alertness declined in both study groups as the length of sleep deprivation increased. Melatonin onset preceded the onset of self‐rated sleepiness in both groups. The time interval between melatonin onset and the onset of sleepiness and alertness offset was significantly greater in the postmenopausal women compared to the pre‐menopausal women. In conclusion, under controlled experimental conditions the timing of the melatonin rhythm was advanced in postmenopausal women altering its phase relationship to subjective alertness and sleepiness.     

Daily Oscillation in Melatonin Synthesis in The Turkey Pineal Gland and Retina: Diurnal and Circadian Rhythms

The aim of the present study was to examine arylalkylamine N‐acetyltransferase (AANAT) activity and melatonin content in the pineal gland and retina as well as the melatonin concentration in plasma of the turkey (Meleagris gallopavo), an avian species in which several physiological processes, including reproduction, are controlled by day length. In order to investigate whether the analyzed parameters display diurnal or circadian rhythmicity, we measured these variables in tissues isolated at regular time intervals from birds kept either under a regular light‐dark (LD) cycle or under constant darkness (DD). The pineal gland and retina of the turkey rhythmically produced melatonin. In birds kept under a daily LD cycle, melatonin levels in the pineal gland and retina were high during the dark phase and low during the light phase. Rhythmic oscillations in melatonin, with high night‐time concentrations, were also found in the plasma. The pineal and retinal melatonin rhythms mirrored oscillations in the activity of AANAT, the penultimate enzyme in the melatonin biosynthetic pathway. Rhythmic oscillations in AANAT activity in the turkey pineal gland and retina were circadian in nature, as they persisted under conditions of constant darkness (DD). Transferring birds from LD into DD, however, resulted in a potent decline in the amplitude of the AANAT rhythm from the first day of DD. On the sixth day of DD, pineal AANAT activity was still markedly higher during the subjective dark than during the subjective light phase; whereas, AANAT activity in the retina did not exhibit significant oscillations. The results indicate that melatonin rhythmicity in the turkey pineal gland and retina is regulated both by light and the endogenous circadian clock. The findings suggest that environmental light may be of primary importance in the maintenance of the high‐amplitude melatonin rhythms in the turkey.     

Structure-based discovery of cellular-active allosteric inhibitors of FAK

In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo[4,3-c][2,1]benzothiazines targeted for the FAK allosteric site were carried out. Based on the X-ray structural analysis of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide 1 with FAK, we designed and prepared 1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases. The optimized compound, N-(4-tert-butylbenzyl)-1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin-8-amine 4,4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC₅₀ = 0.64 μM) and in cellular assays (IC₅₀ = 7.1 μM). These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents.     

Helicobacter pylori flagella: antigenic profile and protective immunity

Reproducible induction of sterilizing immunity, essential for an effective Helicobacter pylori vaccine, remains elusive. As motility is essential for gastric colonization by Helicobacter, we evaluated whether a vaccine targeting flagella induces improved protection. Mice immunized with a vaccine enriched for H. pylori flagella sheath proteins exhibited significantly reduced colonization, equivalent to that observed in mice immunized with whole-cell lysate. Two-dimensional profiles indicated that flagella contain proteins not evident in whole-cell lysate. Moreover, comparison of Western blot profiles using whole-cell lysate antisera revealed striking differences in antigenicity.     

Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors

Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]pteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits >7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model.     

Who owns your body? Legal issues on the ownership of bodily material

Who owns your body and parts removed from it? Can you legally sell your bodily material – or information derived from it? Can you legally prevent other people gaining access to your excised bodily material, including your blood relatives who might need your tissue or genetic information for their own genetic tests? What legal remedies are there if people take or use your bodily material without your consent? And why are the answers to these questions vitally important for scientists?     

Injury-associated induction of GAP-43 expression displays axon branch specificity in rat dorsal root ganglion neurons

Peripheral nerve injury results in the increased synthesis and axonal trasnport of the growth-associated protein GAP-43 in dorsal root ganglion (DRG) neurons, coincident with regenerative growth of the injured peripheral axon branches. To determine wheter the injury-associated signalling mechanism which leads to GAP-43 induction also operates through the central branches of DRG axons, we used immunocytochemistry to compare the expression of GAP-43 in adult rat DRG neurons 2 weeks after dorsal root crush lesions (central axotomy) or peripheral nerve crush lesions (peripheral axotomy). In uninjured ganglia, a subpopulation of smaller DRG neurons expresses moderate levels of GAP-43, whereas larger neurons generally do not. At 2 weeks following peripheral axotomy, virtually all axotomized neurons, large and small, express high levels of GAP-43. At 2 weeks following dorsal root lesions, no increase in GAP-43 expression is detected. Thus, the injury-associated up-regulation of GAP-43 expression in DRG neurons is triggered by a mechanism that is responsive to injury of only the peripheral, and not the central, axon branches. These findings support the hypothesis that GAP-43 induction in DRG neurons is caused by disconnection from peripheral target tissue, not by axon injury per se. © 1993 John Wiley & Sons, Inc.     

Risk-related standard inevitable in assessing competence

In a preceding article, Mark Wicclair suggested that where patient preferences clash with the doctor's recommendations, a minimal understanding of the task at hand, rather than the risks involved, should be the basis for standards of patient competence in decision-making (Bioethics 5(2):91-104, April 1991). Skene, Principal Law Reform Officer of the Victoria, Australia, Law Reform Commission, questions Wicclair's minimum standard from a legal standpoint, pointing out contradictions in the effects of such a standard. Skene concludes that legal protection and the education of both doctors and patients are the most suitable safeguards of patient autonomy.