miR-277 regulates the phase of circadian activity-rest rhythm in Drosophila melanogaster

Circadian clocks temporally organize behaviour and physiology of organisms with a rhythmicity of about 24 h. In Drosophila, the circadian clock is composed of mainly four clock genes: period (per), timeless (tim), Clock (Clk) and cycle (cyc) which constitutes the transcription-translation feedback loop. The circadian clock is further regulated via post-transcriptional and post-translational mechanisms among which microRNAs (miRNAs) are well known post-transcriptional regulatory molecules. Here, we identified and characterized the role of miRNA-277 (miR-277) expressed in the clock neurons in regulating the circadian rhythm. Downregulation of miR-277 in the pacemaker neurons expressing circadian neuropeptide, pigment dispersing factor (PDF) advanced the phase of the morning activity peak under 12 h light: 12 h dark cycles (LD) at lower light intensities and these flies exhibited less robust rhythms compared to the controls under constant darkness. In addition, downregulation of miR-277 in the PDF expressing neurons abolished the Clk gene transcript oscillation under LD. Our study points to the potential role of miR-277 in fine tuning the Clk expression and in maintaining the phase of the circadian rhythm in Drosophila

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Selection for narrow gate of emergence results in correlated sex-specific changes in life history of Drosophila melanogaster

Since the ability to time rhythmic behaviours in accordance with cyclic environments is likely to confer adaptive advantage to organisms, the underlying clocks are believed to be selected for stability in timekeeping over evolutionary time scales. Here we report the results of a study aimed at assessing fitness consequences of a long-term laboratory selection for tighter circadian organisation using fruit fly Drosophila melanogaster populations. We selected flies emerging in a narrow window of 1 h in the morning for several generations and assayed their life history traits such as pre-adult development time, survivorship, adult lifespan and lifetime fecundity. We chose flies emerging during the selection window (in the morning) and another window (in the evening) to represent adaptive and non-adaptive phenotypes, respectively, and examined the correlation of emergence time with adult fitness traits. Adult lifespan of males from the selected populations does not differ from the controls, whereas females from the selected populations have significantly shorter lifespan and produce more eggs during their mid-life compared to the controls. Although there is no difference in the lifespan of males of the selected populations, whether they emerge in morning or evening window, morning emerging females live slightly shorter and lay more eggs during the mid-life stage compared to those emerging in the evening. Interestingly, such a time of emergence dependent difference in fitness is not seen in flies from the control populations. These results, therefore, suggest reduced lifespan and enhanced mid-life reproductive output in females selected for narrow gate of emergence, and a sex-dependent genetic correlation between the timing of emergence and key fitness traits in these populations

Stability of Adult Emergence and Activity/Rest Rhythms in Fruit Flies Drosophila melanogaster under Semi-Natural Condition

Here we report the results of a study aimed at examining stability of adult emergence and activity/rest rhythms under seminatural conditions (henceforth SN), in four large outbred fruit fly Drosophila melanogaster populations, selected for emergence in a narrow window of time under laboratory (henceforth LAB) light/dark (LD) cycles. When assessed under LAB, selected flies display enhanced stability in terms of higher amplitude, synchrony and accuracy in emergence and activity rhythms compared to controls. The present study was conducted to assess whether such differences in stability between selected and control populations, persist under SN where several gradually changing time-cues are present in their strongest form. The study revealed that under SN, emergence waveform of selected flies was modified, with even more enhanced peak and narrower gate-width compared to those observed in the LAB and compared to control populations in SN. Furthermore, flies from selected populations continued to exhibit enhanced synchrony and accuracy in their emergence and activity rhythms under SN compared to controls. Further analysis of zeitgeber effects revealed that enhanced stability in the rhythmicity of selected flies under SN was primarily due to increased sensitivity to light because emergence and activity rhythms of selected flies were as stable as controls under temperature cycles. These results thus suggest that stability of circadian rhythms in fruit flies D. melanogaster, which evolved as a consequence of selection for emergence in a narrow window of time under weak zeitgeber condition of LAB, persists robustly in the face of day-to-day variations in cycling environmental factors of nature

Temperature can entrain egg laying rhythm of Drosophila but may not be a stronger zeitgeber than light

In Drosophila multiple circadian oscillators and behavioral rhythms are known to exist, yet most previous studies that attempted to understand circadian entrainment have focused on the activity/rest rhythm and to some extent the adult emergence rhythm. Egg laying behavior of Drosophila females also follows circadian rhythmicity and has been seen to deviate substantially from the better characterized rhythms in a few aspects. Here we report the findings of our study aimed at evaluating how circadian egg laying rhythm in fruit flies Drosophila melanogaster entrains to time cues provided by light and temperature. Previous studies have shown that activity/rest rhythm of flies entrains readily to light/dark (LD) and temperature cycles (TC). Our present study revealed that egg laying rhythm of a greater percentage of females entrains to TC compared to LD cycles. Therefore, in the specific context of our study this result can be taken to suggest that egg laying clocks of D. melanogaster entrains to TC more readily than LD cycles. However, when TC were presented along with out-of-phase LD cycles, the rhythm displayed two peaks, one occurring close to lights-off and the other near the onset of low temperature phase, indicating that upon entrainment by TC, LD cycles may be able to exert a greater influence on the phase of the rhythm. These results suggest that temperature and light associatively entrain circadian egg laying clocks of Drosophila

Enhanced stability in adult emergence of selected population persists under semi-natural (SN) condition.

<p>(A) Waveform of adult emergence (left panel) in selected (<i>PP</i>) and control (<i>CP</i>) populations averaged across five consecutive cycles under laboratory (LAB). Percentage of flies emerged in 2 h bins are plotted along <i>y</i>-axis and External Time in h along <i>x</i>-axis. The square wave line above the Figure represents 12∶12 h light/dark (LD) cycles under laboratory condition. Peak of emergence in <i>PP</i> and <i>CP</i> populations under LAB (right panel). (B) Waveform of emergence (left panel) of <i>PP</i> and <i>CP</i> populations averaged across five consecutive cycles under SN. Peak of emergence in <i>PP</i> and <i>CP</i> populations under SN (right panel). Upper panels of 2B show average profiles of light (lux), temperature (°C) and humidity (%RH) for the entire duration of the experiment. A greater percentage of <i>PP</i> flies emerge during the selection window compared to <i>CP</i>. Concurrent to the increase in percentage emergence during the selection window there is a decrease in percentage emergence prior-to the selection window, with reduced anticipation to lights-on. Shaded box on the <i>x</i>-axis represents the selection window. Under SN, <i>PP</i> flies sustain robust waveform of emergence with more prominent peak and narrower gate-width. Error bars represent 95% comparison intervals (95%CI) around the mean for visual hypothesis testing. For this assay, ten vials for each of the four replicate populations were used under each environmental condition. The mean values of four replicates and variance in terms of 95% comparison interval (95%CI) were used to draw emergence profiles and error bars.</p

Enhanced robustness in adult emergence of selected population persists under semi-natural (SN).

<p>(A) Circadian waveform of emergence of selected (<i>PP</i>) and control (<i>CP</i>) flies under laboratory (LAB). Percentage of flies that emerged in 2 h bins over five successive cycles is plotted along <i>y</i>-axis and External Time (in h) along <i>x</i>-axis. The square wave indicated above the figure represents 12∶12 h light/dark (LD) cycles. (B) Circadian waveform of emergence under SN. Percentage of flies that emerged in 2 h bins over five successive cycles are plotted along <i>y</i>-axis and External Time in h along <i>x</i>-axis. Upper panels of 1B show daily profiles of light (lux), temperature (^°C) and humidity (%RH) for the entire duration of the experiment. Under LAB, greater percentage of <i>PP</i> flies emerged during the peak which persisted under SN. For this assay, ten vials for each of the four replicate populations were used under each environmental condition. The mean values of four replicates and variance in terms of 95% comparison interval (95%CI) were used to draw emergence profiles and error bars.</p

Selected flies in semi-natural (SN) condition emerge in a narrower gate with enhanced accuracy.

<p>(A) Percentage of flies emerged during the selection window (ExT7-8) under laboratory (LAB) and SN. Higher percentage of flies emerges during the selection window under LAB as well as SN. (B) Gate-width of emergence rhythm in selected (<i>PP</i>) and control (<i>CP</i>) populations. <i>PP</i> flies exhibited narrower emergence gate under SN. (C, D) Synchrony and accuracy of <i>PP</i> and <i>CP</i> flies under LAB and SN. <i>PP</i> flies exhibit greater synchrony and accuracy compared to controls under both conditions. All other details are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050379#pone-0050379-g002" target="_blank">Figure 2</a>.</p