Cry1 expression during postnatal development is critical for the establishment of normal circadian period.

The mammalian circadian system generates an approximate 24-h rhythm through a complex autoregulatory feedback loop. Four genes, Period1 (Per1), Period2 (Per2), Cryptochrome1 (Cry1), and Cryptochrome2 (Cry2), regulate the negative feedback within this loop. Although these proteins have distinct roles within the core circadian mechanism, their individual functions are poorly understood. Here, we used a tetracycline trans-activator system (tTA) to examine the role of transcriptional oscillations in Cry1 and Cry2 in the persistence of circadian activity rhythms. We demonstrate that rhythmic Cry1 expression is an important regulator of circadian period. We then define a critical period from birth to postnatal day 45 (PN45) where the level of Cry1 expression is critical for setting the endogenous free running period in the adult animal. Moreover, we show that, although rhythmic Cry1 expression is important, in animals with disrupted circadian rhythms overexpression of Cry1 is sufficient to restore normal behavioral periodicity. These findings provide new insights into the roles of the Cryptochrome proteins in circadian rhythmicity and further our understanding of the mammalian circadian clock.

Characterization of Stress Responses in a Drosophila Model of Werner Syndrome.

As organisms age, their resistance to stress decreases while their risk of disease increases. This can be shown in patients with Werner syndrome (WS), which is a genetic disease characterized by accelerated aging along with increased risk of cancer and metabolic disease. WS is caused by mutations in WRN, a gene involved in DNA replication and repair. Recent research has shown that WRN mutations contribute to multiple hallmarks of aging including genomic instability, telomere attrition, and mitochondrial dysfunction. However, questions remain regarding the onset and effect of stress on early aging. We used a fly model of WS (WRNexoΔ) to investigate stress response during different life stages and found that stress sensitivity varies according to age and stressor. While larvae and young WRNexoΔ adults are not sensitive to exogenous oxidative stress, high antioxidant activity suggests high levels of endogenous oxidative stress. WRNexoΔ adults are sensitive to stress caused by elevated temperature and starvation suggesting abnormalities in energy storage and a possible link to metabolic dysfunction in WS patients. We also observed higher levels of sleep in aged WRNexoΔ adults suggesting an additional adaptive mechanism to protect against age-related stress. We suggest that stress response in WRNexoΔ is multifaceted and evokes a systemic physiological response to protect against cellular damage. These data further validate WRNexoΔ flies as a WS model with which to study mechanisms of early aging and provide a foundation for development of treatments for WS and similar diseases.

Lower variability in female students than male students at multiple timescales supports the use of sex as a biological variable in human studies.

BACKGROUND: Men have been, and still are, included in more studies than women, in large part because of the lingering belief that ovulatory cycles result in women showing too much variability to be economically viable subjects. This belief has scientific and social consequences, and yet, it remains largely untested. Recent work in rodents has shown either that there is no appreciable difference in overall variability across a wealth of traits, or that in fact males may show more variability than females. METHODS: We analyzed learning management system logins associated to gender records spanning 2 years from 13,777 students at Northeastern Illinois University. These data were used to assess variability in daily rhythms in a heterogeneous human population. RESULTS: At the population level, men are more likely than women to show extreme chronotypes (very early or very late phases of activity). Men were also found to be more variable than women across and within individuals. Variance correlated negatively with academic performance, which also showed a gender difference. Whereas a complaint against using female subjects is that their variance is the driver of statistical sex differences, only 6% of the gender performance difference is potentially accounted for by variance, suggesting that variability is not the driver of sex differences here. CONCLUSIONS: Our findings do not support the idea that women are more behaviorally variable than men and may support the opposite. Our findings support including sex as a biological variable and do not support variance-based arguments for the exclusion of women as research subjects.

Evidence for premature aging in a Drosophila model of Werner syndrome.

Werner syndrome (WS) is an autosomal recessive progeroid disease characterized by patients' early onset of aging, increased risk of cancer and other age-related pathologies. WS is caused by mutations in WRN, a RecQ helicase that has essential roles responding to DNA damage and preventing genomic instability. While human WRN has both an exonuclease and helicase domain, Drosophila WRNexo has high genetic and functional homology to only the exonuclease domain of WRN. Like WRN-deficient human cells, Drosophila WRNexo null mutants (WRNexoΔ) are sensitive to replication stress, demonstrating mechanistic similarities between these two models. Compared to age-matched wild-type controls, WRNexoΔ flies exhibit increased physiological signs of aging, such as shorter lifespans, higher tumor incidence, muscle degeneration, reduced climbing ability, altered behavior, and reduced locomotor activity. Interestingly, these effects are more pronounced in females suggesting sex-specific differences in the role of WRNexo in aging. This and future mechanistic studies will contribute to our knowledge in linking faulty DNA repair mechanisms with the process of aging.

Mapping behaviorally relevant light pollution levels to improve urban habitat planning.

Artificial nighttime lights have important behavioral and ecological effects on wildlife. Combining laboratory and field techniques, we identified behaviorally relevant levels of nighttime light and mapped the extent of these light levels across the city of Chicago. We began by applying a Gaussian finite mixture model to 998 sampled illumination levels around Chicago to identify clusters of light levels. A simplified sample of these levels was replicated in the laboratory to identify light levels at which C57BL/6J mice exhibited altered circadian activity patterns. We then used camera trap and high-altitude photographic data to compare our field and laboratory observations, finding activity pattern changes in the field consistent with laboratory observations. Using these results, we mapped areas across Chicago exposed to estimated illumination levels above the value associated with statistically significant behavioral changes. Based on this measure, we found that as much as 36% of the greenspace in the city is in areas illuminated at levels greater than or equal to those at which we observe behavioral differences in the field and in the laboratory. Our findings provide evidence that artificial lighting patterns may influence wildlife behavior at a broad scale throughout urban areas, and should be considered in urban habitat planning.

3.4 million real-world learning management system logins reveal the majority of students experience social jet lag correlated with decreased performance.

Misalignments between endogenous circadian rhythms and the built environment (i.e., social jet lag, SJL) result in learning and attention deficits. Currently, there is no way to assess the impact of SJL on learning outcomes of large populations as a response to schedule choices, let alone to assess which individuals are most negatively impacted by these choices. We analyzed two years of learning management system login events for 14,894 Northeastern Illinois University (NEIU) students to investigate the capacity of such systems as tools for mapping the impact of SJL over large populations while maintaining the ability to generate insights about individuals. Personal daily activity profiles were validated against known biological timing effects, and revealed a majority of students experience more than 30 minutes of SJL on average, with greater amplitude correlating strongly with a significant decrease in academic performance, especially in people with later apparent chronotypes. Our findings demonstrate that online records can be used to map individual- and population-level SJL, allow deep mining for patterns across demographics, and could guide schedule choices in an effort to minimize SJL's negative impact on learning outcomes.

Evaluating the role of temperature in the reproduction of the yellow stingray (Urobatis jamaicensis).

We conducted a temperature-dependent reproductive study on Yellow Stingrays (Urobatis jamaicensis) at the John G. Shedd Aquarium, Chicago, Illinois. A group of eight and six female rays were mated in 22°C ("cold") and 27°C ("warm") water, respectively, over a two-year period. Mating behavior, gestation length, pup yields, body condition indices, and activity levels were compared throughout both temperature trials. Mating behavior (e.g., pre-copulatory pursuits and behavior) did not differ between temperature trials. Cold trial gestation was incomplete and yielded no pups, while the warm trial resulted in three successful births and one stillborn birth. Body condition indices and overall activity were significantly decreased in the cold trials. These data suggest consequences for rearing Yellow Stingrays in cooler water and should aid in successful reproduction of U. jamaicensis at zoos and aquariums.

Circadian rhythms affect electroretinogram, compound eye color, striking behavior and locomotion of the praying mantis Hierodula patellifera.

Many behaviors and physiological processes oscillate with circadian rhythms that are synchronized to environmental cues (e.g. light onset), but persist with periods of ~24 h in the absence of such cues. We used a multilevel experimental approach to assess whether circadian rhythms modulate several aspects of the visual physiology and behavior of the praying mantis Hierodula patellifera. We used electroretinograms (ERGs) to assess compound eye sensitivity, colorimetric photographic analyses to assess compound eye color changes (screening pigment migration), behavioral assays of responsiveness to computer-generated prey-like visual stimuli and analyses of locomotor activity patterns on a modified treadmill apparatus. Our results indicate that circadian clocks control and/or modulate each of the target behaviors. Strong rhythms, persisting under constant conditions, with periods of ~24 h were evident in photoreceptor sensitivity to light, appetitive responsiveness to prey-like stimuli and gross locomotor activity. In the first two cases, responsiveness was highest during the subjective night and lowest during the subjective day. Locomotor activity was strongly clustered around the transition time from day to night. In addition, pigment migration and locomotor behavior responded strongly to light:dark cycles and anticipated the light-dark transition, suggesting that the circadian clocks modulating both were entrained to environmental light cues. Together, these data indicate that circadian rhythms operate at the cellular, cellular systems and organismal level in H. patellifera. Our results represent an intriguing first step in uncovering the complexities of circadian rhythms in the Mantodea.