Study objectivesTo determine the effect of light exposure on subsequent sleep characteristics under ambulatory field conditions.MethodsTwenty healthy participants were fitted with ambulatory polysomnography (PSG) and wrist-actigraphs to assess light exposure, rest–activity, sleep quality, timing, and architecture. Laboratory salivary dim-light melatonin onset was analyzed to determine endogenous circadian phase.ResultsLater circadian clock phase was associated with lower intensity (R2 = 0.34, χ2(1) = 7.19, p < .01), later light exposure (quadratic, controlling for daylength, R2 = 0.47, χ2(3) = 32.38, p < .0001), and to later sleep timing (R2 = 0.71, χ2(1) = 20.39, p < .0001). Those with later first exposure to more than 10 lux of light had more awakenings during subsequent sleep (controlled for daylength, R2 = 0.36, χ2(2) = 8.66, p < .05). Those with later light exposure subsequently had a shorter latency to first rapid eye movement (REM) sleep episode (R2 = 0.21, χ2(1) = 5.77, p < .05). Those with less light exposure subsequently had a higher percentage of REM sleep (R2 = 0.43, χ2(2) = 13.90, p < .001) in a clock phase modulated manner. Slow-wave sleep accumulation was observed to be larger after preceding exposure to high maximal intensity and early first light exposure (p < .05).ConclusionsThe quality and architecture of sleep is associated with preceding light exposure. We propose that light exposure timing and intensity do not only modulate circadian-driven aspects of sleep but also homeostatic sleep pressure. These novel ambulatory PSG findings are the first to highlight the direct relationship between light and subsequent sleep, combining knowledge of homeostatic and circadian regulation of sleep by light. Upon confirmation by interventional studies, this hypothesis could change current understanding of sleep regulation and its relationship to prior light exposure.Clinical trial detailsThis study was not a clinical trial. The study was ethically approved and nationally registered (NL48468.042.14).

Voles are small herbivorous rodents that can display both circadian activity rhythms (~24-h periodicity) and ultradian activity rhythms (~1- to 6-h periodicity). Ultradian rhythms are observed on an individual level, but also in synchronized populations. Ultradian rhythm period has been suggested to be influenced by energy balance, but the underlying mechanisms of ultradian rhythmicity are poorly understood. We manipulated energy balance by implementing the “work-for-food” paradigm, in which small rodents are exposed to increasing levels of food scarcity at different ambient temperatures in the laboratory. Photoperiodical spring-programmed voles on high workload changed their nocturnal circadian activity and body temperature rhythm to ultradian patterns, indicating that a negative energy balance induces ultradian rhythmicity. This interpretation was confirmed by the observation that ultradian patterns arose earlier at low temperatures. Interestingly, a positive relationship between ultradian period length and workload was observed in tundra voles. Spectral analysis revealed that the power of ultradian rhythmicity increased at high workload, whereas the circadian component of running wheel activity decreased. This study shows that the balance between circadian and ultradian rhythmicity is determined by energy balance, confirming flexible circadian and ultradian rhythms in females and males of 2 different vole species: the common vole ( Microtus arvalis) and the tundra vole ( Microtus oeconomus).

statement: Development of the neuroendocrine system driving photoperiodic 34 responses in gonadal and somatic growth differ between the common and the tundra vole, 35 indicating that they use a different breeding strategy. 36 37 List of abbreviations: 38 ARC -arcuate nucleus 39 Dio2 -iodothyronine-deiodinase 2 40 Dio3 -iodothyronine-deiodinase 3 41 Dnmt1 -DNA methyltransferase 1 42 Dnmt3a -DNA methyltransferase 3a 43 GH -growth hormone 44 GnRH -gonadotropin-releasing hormone 45 Kiss1 -Kisspeptin 46 KNDy -kisspeptin/neurokininB/Dynorphin 47 PNESphotoperiodic neuroendocrine system 50 PTpars tuberalis 51 SCN -suprachiasmatic nucleus 52 SPshort photoperiod 53 Tsh -thyroid-stimulating-hormone- subunit 54 55 56 57 58 59 60 61 62 63 64 65 66 Abstract 67To optimally time reproduction, seasonal mammals use a photoperiodic neuroendocrine 68 system (PNES) that measures photoperiod and subsequently drives reproduction. To adapt to 69 late spring arrival at northern latitudes, a lower photoperiodic sensitivity and therefore a 70 higher critical photoperiod for reproductive onset is necessary in northern species to arrest 71 reproductive development until spring onset. Temperature-photoperiod relationships, and 72 hence food availability-photoperiod relationships, are highly latitude dependent. Therefore, 73we predict PNES sensitivity characteristics to be latitude-dependent. Here, we investigated 74 photoperiodic responses at different times during development in northern-(tundra/root vole, 75Microtus oeconomus) and southern vole species (common vole, Microtus arvalis) exposed to 76 constant short (SP) or long photoperiod (LP). 77 M. oeconomus grows faster under LP, whereas no photoperiodic effect on somatic 78 growth is observed in M. arvalis. Contrastingly, gonadal growth is more sensitive to 79 photoperiod in M. arvalis, suggesting that photoperiodic responses in somatic and gonadal 80 growth can be plastic, and might be regulated through different mechanisms. In both species, 81 thyroid-stimulating-hormone- subunit (Tsh) and iodothyronine-deiodinase 2 (Dio2) 82 expression is highly increased under LP, whereas Tshr and Dio3 decreases under LP. High 83 Tshr levels in voles raised under SP may lead to increased sensitivity to increasing 84 photoperiods later in life. The higher photoperiodic induced Tshr response in M. oeconomus 85 suggests that the northern vole species might be more sensitive to TSH when raised under SP. 86 Species differences in developmental programming of the PNES, which is dependent 87 on photoperiod early in development, may form part divergent breeding strategies evolving 88 as part of latitudinal adaptation. 89 90

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Seasonal timing of reproduction in voles is driven by photoperiod. Here we hypothesize that a negative energy balance can modify spring-programmed photoperiodic responses in the hypothalamus, controlling reproductive organ development. We manipulated energy balance by the ‘work-for-food’ protocol, in which voles were exposed to increasing levels of food scarcity at different ambient temperatures under long photoperiod. We reveal that in common voles (Microtus arvalis) and tundra voles (Microtus oeconomus), photoperiodic induced pars tuberalis thyroid-stimulating hormone β-subunit (Tshβ) expression is reduced to potentially inhibit gonadal development when food is scarce. Reduction in gonadal size is more pronounced in tundra voles, in which anterior hypothalamic Kiss1 is additionally downregulated, especially in males. Low temperature additionally leads to decreased hypothalamic Rfrp expression, which potentially may facilitate further suppression of gonadal growth. Shutting off the photoperiodic-axis when food is scarce in spring may be an adaptive response to save energy, leading to delayed reproductive organ development until food resources are sufficient for reproduction, lactation and offspring survival. Defining the mechanisms through which metabolic cues modify photoperiodic responses will be important for a better understanding of how environmental cues impact reproduction.

To optimally time reproduction, seasonal mammals use a photoperiodic neuroendocrine system (PNES) that measures photoperiod and subsequently drives reproduction. To adapt to late spring arrival at northern latitudes, a lower photoperiodic sensitivity and therefore a higher critical photoperiod for reproductive onset is necessary in northern species to arrest reproductive development until spring onset. Temperature-photoperiod relationships, and hence food availability-photoperiod relationships, are highly latitude dependent. Therefore, we predict PNES sensitivity characteristics to be latitude-dependent. Here, we investigated photoperiodic responses at different times during development in northern (tundra/root vole, Microtus oeconomus) and southern vole species (common vole, Microtus arvalis) exposed to constant short (SP) or long photoperiod (LP). Although, the tundra vole grows faster under LP, no photoperiodic effect on somatic growth is observed in the common vole. Contrastingly, gonadal growth is more sensitive to photoperiod in the common vole, suggesting that photoperiodic responses in somatic and gonadal growth can be plastic, and might be regulated through different mechanisms. In both species, thyroid-stimulating-hormone-β subunit (Tshβ) and iodothyronine- deiodinase 2 (Dio2) expression is highly increased under LP, whereas Tshr and Dio3 decreases under LP. High Tshr levels in voles raised under SP may lead to increased sensitivity to increasing photoperiods later in life. The higher photoperiodic induced Tshr response in tundra voles suggests that the northern vole species might be more sensitive to TSH when raised under SP. In conclusion, species differences in developmental programming of the PNES, which is dependent on photoperiod early in development, may form different breeding strategies evolving as part of latitudinal adaptation.

23Meiosis is essential for sexual reproduction and key to the generation of genetic 24 diversity. To reveal the robustness of meiocyte differentiation and progression 25 through meiosis, we have here established a live cell imaging setup to follow the 26 dynamics of individual male meiocytes in Arabidopsis. Our method is based on the 27 concomitant visualization of microtubules and a meiotic cohesion subunit that 28 allowed following five cellular parameters: cell shape, nucleus position, nucleolus 29 position, chromatin condensation and microtubule array. We find that the states of 30 these parameters are not randomly associated and identify 11 states, referred to as 31 landmarks, that occur much more frequently than closely related states, indicating 32 that they are convergent points of meiotic progression. With this, the here-presented 33 landmark system represents a novel method to analyze meiosis not only allowing a 34 high-temporal dissection but also providing new criteria to evaluate mutants or 35 environmental effects on meiosis. 36 37 38 First, we selected inflorescences and removed all but one young flower 128 primordium presumably containing meiotic stages as indicated by its round shape 129 and an approximate diameter of 0.4-0.6 mm ( Figure 1B), corresponding to stage 9 of 130 flower development (Smyth et al., 1990). Next, the upper sepal was removed giving 131 access to two of the six anthers since the petals are shorter than the anthers at this 132 floral stage. Finally, the bud along with the pedicel and a few millimeters of the stem 133 was embedded into Arabidopsis Apex Culture Medium (ACM) and stabilized with a 134 drop of agarose ( Figure 1A,B). In agreement with the previous analysis of the SAM, 135 we found that the flower buds stayed alive on the ACM medium for up to seven days 136 during which flowers grew and developed normally ( Figure 1C). 137Imaging was performed with an up-right confocal laser scanning microscopy 138 equipped with a water immersion objective. The entire flower bud was submerged in 139 water and the objective was brought into direct contact with the sample (Figure 1A).

Previously unknown correspondence between Nadya Nikolaevna Ladygina-Kohts, author of The Chimpanzee Child and the Human Child (1935), and Harry Harlow shows a reciprocal interest in, and admiration for, each other's work. In 1960 and 1961, they exchanged some 9 letters as well as numerous reprints and publications. The correspondence shows that Ladygina-Kohts and Harlow had been following each other's work for years and that Ladygina-Kohts's work may have been one of the major inspirations to Harlow's primate program.