Project description:In the present study, we sought to determine the degree of circadian misalignments of hormonal and transcriptional rhythms with the timing of sleep-wake behavior on days off in day-shift and night-shift hospital nurses. We conducted a genome-wide microarray analysis on RNA isolated from PBMCs to examine individual variability of transcriptional rhythms.
Project description:Circadian misalignment between sleep and behavioral/feeding rhythms is thought to lead to various health impairments in shift workers. Therefore, we investigated how shift work leads to genome-wide circadian dysregulation in hospital nurses. Female nurses from the University of Alabama at Birmingham (UAB) Hospital working night shift ( n = 9; 29.6 ± 11.4 y) and day shift ( n = 8; 34.9 ± 9.4 y) participated in a 9-day study measuring locomotor activity and core body temperature (CBT) continuously. Additionally, cortisol and melatonin were assayed and peripheral blood mononuclear cells (PBMCs) were harvested for RNA extraction every 3 h on a day off from work. We saw phase desynchrony of core body temperature, peak cortisol, and dim light melatonin onset in individual night-shift subjects compared with day-shift subjects. This variability was evident even though day- and night-shift nurses had similar sleep timing and scheduled meal times on days off. Surprisingly, the phase and rhythmicity of the expression of the clock gene, PER1, in PBMCs were similar for day-shift and night-shift subjects. Genome-wide microarray analysis of PBMCs from a subset of nurses revealed distinct gene expression patterns between night-shift and day-shift subjects. Enrichment analysis showed that day-shift subjects expressed pathways involved in generic transcription and regulation of signal transduction, whereas night-shift subjects expressed pathways such as RNA polymerase I promoter opening, the matrisome, and endocytosis. In addition, there was large variability in the number of rhythmic transcripts among subjects, regardless of shift type. Interestingly, the amplitude of the CBT rhythm appeared to be more consistent with the number of cycling transcripts for each of the 6 subjects than was melatonin rhythm. In summary, we show that shift-work patterns affect circadian alignment and gene expression in PBMCs.
Project description:We investigated genome-wide DNA methylation of newly emerged queens, newly emerged workers, adult nurses, adult foragers and adult reverted nurses using comprehensive high throughput arrays for relative methylation (CHARM) We used custom Nimblegen microarrays We isolated genomic DNA from newly emerged queens, newly emerged workers, adult continuous nurses, adult continuous foragers and adult reverted nurses hybridized to custom-designed Nimblegen microarrays (CHARM arrays). Multiple brains were pooled for each sample and used for the genome-wide DNA methylation analysis.
Project description:Shift work misaligns the circadian clock and leads to an increased risk of cancer, cardiovascular diseases, and metabolic disorders. Furthermore, food consumed during the rest phase is a major contributor to this misalignment, as food access restricted to the endogenous active phase, at night, prevents against the adverse effects of shift work on obesity and diabetes in rats. In this study, we aimed to investigate the molecular mechanisms by which shift work and food consumption contribute to an increased risk of cardiovascular disorders. To this end, we used a model of shift work in rats, whereby animals are exposed to a 12:12 light:dark cycle and are forced to be active for eight-hours during their natural rest phase during the day, Monday to Friday for five consecutive weeks. Given the preventive effects of temporal restriction of food intake, a group of shift worker rats with food access restricted to the night was included in addition to controls and shift workers. To gain insight into the molecular underpinnings of shift-work associated cardiovascular pathologies, we performed RNA-Seq analysis and Picrosirius Red staining in rat hearts. Our results show that shift work in rats, regardless of the time of food consumption, have an increase in collagen deposition in the heart. In addition, the expression of many genes encoding key fibrotic pathways was found to be up-regulated in shift worker rats that had their food restricted to the active phase. Altogether, our results suggest that five weeks of shift work in rats is capable of inducing cardiovascular disease through an up-regulation of collagen deposition in the heart.
Project description:Eight healthy human subjects were enrolled in a 6-day simulated shift work protocol. Blood samples were collected during the two 24-hour measurement periods. Blood samples were collected every 4 hours during both measurement periods. Subjects entered the lab on Day 1. At the start of Day 2, the first 24-hour measurement period was started. Subjects slept according to their habitual sleep/wake schedule, followed by a 16-hour constant posture procedure. On days 3-6, the sleep period was delayed by 10 hours. Following the third night on this schedule, subjects underwent another 24-hour measurement period. During both measurement periods, 7 blood samples were collected and PBMCs were isolated. mRNA was extracted, labelled, and hybridized to microarrays.
Project description:We investigated genome-wide DNA methylation of newly emerged queens, newly emerged workers, adult nurses, adult foragers and adult reverted nurses using comprehensive high throughput arrays for relative methylation (CHARM) We used custom Nimblegen microarrays
Project description:Increased breast cancer risk has been reported in some night shift (NS) workers but underlying biological mechanisms are still unclear. We assessed the association between NS work and DNA methylation of tumor suppressor (TP53, CDKN2A, BRCA1, BRCA2) and estrogen receptor (ESR1, ESR2) genes, methylation of repetitive elements (LINE-1, Alu), and telomere length (TL). Forty six female nurses employed in NS for at least two years were matched by age (30-45 years) and length of service (≥1 year) with 51 female colleagues not working in NS. Each subject underwent a semi-structured interview and gave a blood sample. We applied linear regression and spline models adjusted for age, BMI, smoking habit, oral contraceptive use, parity and marital status/age at marriage. Currently working in NS was associated with ESR1 hypomethylation (β: -1.85 (95%CI: -3.03; -0.67), p = 0.003). In current and former NS workers we observed TP53 (-0.93 (-1.73; -0.12), p = 0.03) and BRCA1 (-1.14 (-1.71; -0.58), p <0.001) hypomethylation. We found an increase between TL and number of years in NS in subjects employed in NS <12 years (0.06 (0.03; 0.09), p <0.001), while a decrease if employed in NS ≥12 years (-0.07 -0.10; -0.04), p <0.001). Our findings show NS-associated markers potentially involved in cellular aging, genomic instability, and cancer development.
Project description:Shift work can lead to circadian desynchronization due to temporary misalignment between working hours and physiological and behavioral functioning, resulting in compromised health, insomnia, worsening of sleep quality, reduced ability to work during waking hours, and increased cardiovascular risk. We evaluated the effects of shift work on the rest-activity circadian rhythm (RAR) and health status of Italian orthopaedic nurses. The study population was 59 nurses: 44 worked the night shift and 15 worked the day shift. All carried out continuous 5-day actigraphic monitoring to assess RAR, including both the working and the rest period. The rhythmometric analysis showed that, during the working period, the night shift nurses had a significantly lower amplitude than the day shift nurses (p < 0.001), and the acrophase was significantly different between the two groups (p < 0.01). When we stratified the two groups by median body mass index (<25 kg/m2 normal weight and ≥25 kg/m2 overweight), during the working period, we noted a significantly lower amplitude for both the normal weight and the overweight nurses who worked the night shift (p < 0.01 and p < 0.001, normal weight and overweight respectively). The current findings suggest the need for further study of the relationship between activity levels and shift work.