This study quantifies sex differences in the diurnal and circadian variation of sleep and waking while controlling for menstrual cycle phase and hormonal contraceptive use. We compared the diurnal ...and circadian variation of sleep and alertness of 8 women studied during two phases of the menstrual cycle and 3 women studied during their midfollicular phase with that of 15 men. Participants underwent an ultradian sleep–wake cycle (USW) procedure consisting of 36 cycles of 60-min wake episodes alternating with 60-min nap opportunities. Core body temperature (CBT), salivary melatonin, subjective alertness, and polysomnographically recorded sleep were measured throughout this procedure. All analyzed measures showed a significant diurnal and circadian variation throughout the USW procedure. Compared with men, women demonstrated a significant phase advance of the CBT but not melatonin rhythms, as well as an advance in the diurnal and circadian variation of sleep measures and subjective alertness. Furthermore, women experienced an increased amplitude of the diurnal and circadian variation of alertness, mainly due to a larger decline in the nocturnal nadir. Our results indicate that women are likely initiating sleep at a later circadian phase than men, which may be one factor contributing to the increased susceptibility to sleep disturbances reported in women. Lower nighttime alertness is also observed, suggesting a physiological basis for a greater susceptibility to maladaptation to night shift work in women.
Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may ...be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.
This study of depressed outpatients (N = 43) examined daily stress-sadness reactivity and the cortisol awakening response (CAR) as moderators of the relationship between self-critical (SC) ...perfectionism and depression over one year. Participants completed perfectionism measures at baseline (Time 1), daily diaries and salivary sampling six months later (Time 2), and an interviewer-rated depression measure at Time 1, Time 2, and one year after baseline (Time 3). Hierarchical multiple regression analyses of moderator effects demonstrated that patients with higher SC perfectionism and higher levels of daily stress-sadness reactivity (i.e., greater increases in daily sadness in response to increases in daily stress) had less improvement in depressive symptoms at Time 3 relative to those of other patients, adjusting for the effects of Time 1 and Time 2 depression. Furthermore, higher SC perfectionism in conjunction with an elevated CAR predicted higher levels of depression at Time 3. In addition, lower SC perfectionism in combination with higher levels of stress-sadness reactivity/CAR was associated with the lowest levels of depression at Time 3. These findings highlight the importance of targeting dysfunctional self-critical characteristics that exacerbate the impact of heightened stress-sadness reactivity and CAR to generate better treatment outcomes for patients with higher SC perfectionism.
Public Significance Statement
This study demonstrates that self-critical perfectionism predicts less improvement in depression for individuals with higher stress-sadness reactivity or a higher cortisol awakening response. The findings highlight the importance of considering perfectionism, stress reactivity, and cortisol in the treatment of depression.
Abstract Objectives Women with premenstrual dysphoric disorder (PMDD) experience disturbed mood, altered melatonin circadian rhythms, and frequent reports of insomnia during the luteal phase (LP) of ...their menstrual cycle. In this study we aimed to investigate nocturnal polysomnographic (PSG) sleep across the menstrual cycle in PMDD women and controls. Methods Seven PMDD women who indicated insomnia during LP, and five controls, spent every third night throughout a complete menstrual cycle sleeping in the laboratory. Results In PMDD and controls progesterone and core body temperature (BTcore ) were elevated during LP compared to the follicular phase (FP). Stage 2 sleep showed a significant main effect of menstrual phase and was significantly increased during mid-LP compared to early-FP in both groups. Rapid eye movement (REM) sleep for both groups was decreased during early-LP compared to early-FP. Slow wave sleep (SWS) was significantly increased, and melatonin significantly decreased, in PMDD women compared to controls. Conclusions PMDD women who experience insomnia during LP had decreased melatonin secretion and increased SWS compared to controls. The sleep and melatonin findings in PMDD women may be functionally linked. Results also suggest an altered homeostatic regulation of the sleep–wake cycle in PMDD, perhaps implicating melatonin in the homeostatic process of sleep–wake regulation.
The ductility and exhibition of the multiple, fine, self-controlled cracking of strain-hardening cementitious composites (SHCCs) under tension has made them attractive for enhancing the durability of ...civil infrastructure. These fine cracks are key to preventing the ingress of water and harmful chemicals into the structure and thereby achieving steel reinforcement. However, several studies have suggested that the short-term fine cracks shown in the laboratory may end up exceeding the acceptable crack widths that are specified in design codes when SHCC members are subjected to sustained constant loads. In real structures, however, the load is also shared by the steel reinforcement in the member, so the SHCC within may not be under a constant load; therefore, the crack widening will not be as severe. This study focuses on the creep behaviour of SHCCs when they are applied as an external layer on reinforced concrete to enhance durability. A novel approach to simulate various stress-strain regimes in such systems is developed by using a fixture to share a sustained moment exclusively between a reinforcement member and SHCC. The developed load-sharing system allows stresses within the reinforcement and SHCC to be monitored against time during the imposed loading, while ensuring access to the SHCC layer for instrumentation and monitoring of strain/cracking. The time-dependent widening of cracks in the SHCC layer is found to be much less significant than that under constant loading, so resistance to water/chemical penetration can still be ensured in the long term. The obtained information on the variation in stress, strain, and crack opening with time will be useful for the development of a general model for the creep behaviour of SHCC members.
Chloroplasts are the sites for photosynthesis, and two Golden2-like factors act as transcriptional activators of chloroplast development in rice (Oryza sativa L.) and maize (Zea mays L.). Rice OsGLK1 ...and OsGLK2 are orthologous to maize ZmGLK1 (ZmG1) and ZmGLK2 (ZmG2), respectively. However, while rice OsGLK1 and OsGLK2 act redundantly to regulate chloroplast development in mesophyll cells, maize ZmG1 and ZmG2 are functionally specialized and expressed in different cell-specific manners. To boost rice chloroplast development and photosynthesis, we generated transgenic rice plants overexpressing ZmG1 and ZmG2, individually or simultaneously, with constitutive promoters (pZmUbi::ZmG1 and p35S::ZmG2) or maize promoters (pZmG1::ZmG1, pZmG2::ZmG2, and pZmG1::ZmG1/pZmG2::ZmG2). Both ZmG1 and ZmG2 genes were highly expressed in transgenic rice leaves. Moreover, ZmG1 and ZmG2 showed coordinated expression in pZmG1::ZmG1/pZmG2::ZmG2 plants. All Golden2-like (GLK) transgenic plants had higher chlorophyll and protein contents, Rubisco activities and photosynthetic rates per unit leaf area in flag leaves. However, the highest grain yields occurred when maize promoters were used; pZmG1::ZmG1, pZmG2::ZmG2, and pZmG1::ZmG1/pZmG2::ZmG2 transgenic plants showed increases in grain yield by 51%, 47%, and 70%, respectively. In contrast, the pZmUbi::ZmG1 plant produced smaller seeds without yield increases. Transcriptome analysis indicated that maize GLKs act as master regulators promoting the expression of both photosynthesis-related and stress-responsive regulatory genes in both rice shoot and root. Thus, by promoting these important functions under the control of their own promoters, maize GLK1 and GLK2 genes together dramatically improved rice photosynthetic performance and productivity. A similar approach can potentially improve the productivity of many other crops.
The Senegalese cobra, Naja senegalensis, is a non-spitting cobra species newly erected from the Naja haje complex. Naja senegalensis causes neurotoxic envenomation in Western Africa but its venom ...properties remain underexplored. Applying a protein decomplexation proteomic approach, this study unveiled the unique complexity of the venom composition. Three-finger toxins constituted the major component, accounting for 75.91% of total venom proteins. Of these, cardiotoxin/cytotoxin (~53%) and alpha-neurotoxins (~23%) predominated in the venom proteome. Phospholipase A2, however, was not present in the venom, suggesting a unique snake venom phenotype found in this species. The venom, despite the absence of PLA2, is highly lethal with an intravenous LD50 of 0.39 µg/g in mice, consistent with the high abundance of alpha-neurotoxins (predominating long neurotoxins) in the venom. The hetero-specific VINS African Polyvalent Antivenom (VAPAV) was immunoreactive to the venom, implying conserved protein antigenicity in the venoms of N. senegalensis and N. haje. Furthermore, VAPAV was able to cross-neutralize the lethal effect of N. senegalensis venom but the potency was limited (0.59 mg venom completely neutralized per mL antivenom, or ~82 LD50 per ml of antivenom). The efficacy of antivenom should be further improved to optimize the treatment of cobra bite envenomation in Africa.
To broaden the applications of fiber reinforced polymer (FRP) reinforced concrete structures under marine environments, it is crucial to gain a fundamental understanding of their short- and long-term ...performance. In this study, the effectiveness of the proposed multi-scale simulation platform, which incorporates the proposed degradation model of FRP bars, is quantitatively assessed via the comparison between the predicted results and experimental load-displacement curves under different marine conditions (continuous immersion, wet-dry cycling and subtropical marine atmosphere). The spatially physical, chemical and mechanical information, such as pH value, moisture, hydration degree, strength, porosity during the exposure was also revealed. Finally, the long-term structural performance of FRP-reinforced concrete beams exposed to the predefined environmental conditions over durations of 20, 50 and 100 years are assessed using the multi-scale simulation platform. After 50 years of exposure, the load-bearing capacity of GFRP-reinforced concrete beams was found to decrease by 35.8 % in immersion conditions and by 17.9 % in subtropical marine atmosphere. The degradation of the load-bearing capacity in the case of 100 years exposure to subtropical marine atmosphere was found to be less severe than that (23.1 %) in the case of 50-year immersion. These findings not only deepen our understanding of the material and structural properties of FRP-reinforced concrete beams under various environmental conditions, but also validate the effectiveness of the proposed multi-scale platform.
•A degradation model for FRP bar was proposed and validated via experimental data.•A multi-scale simulation platform was developed for FRP reinforced concrete.•The short-/long-term performance under different marine conditions was studied.•The simulation platform revealed physical, chemical, and mechanical information.•Immersion led to more severe degradation than subtropical marine atmosphere.
In the present article, we report on two studies performed in young human populations which tested the cognitive impact of glucocorticoids (GC) in situations of decreased or increased ratio of ...mineralocorticoid (MR) and glucocorticoid (GR) receptor occupation. In the first study, we used a hormone replacement protocol in which we pharmacologically decreased cortisol levels by administration of metyrapone and then restored baseline cortisol levels by a subsequent hydrocortisone replacement treatment. Memory function was tested after each pharmacological manipulation. We observed that metyrapone treatment significantly impaired delayed recall, while hydrocortisone replacement restored performance at placebo level. In the second study, we took advantage of the circadian variation of circulating levels in cortisol and tested the impact of a bolus injection of 35 mg of hydrocortisone in the late afternoon, at a time of very low cortisol concentrations. In a previous study with young normal controls, we injected a similar dose of hydrocortisone in the morning, at the time of the circadian peak, and reported detrimental effects of GC on cognitive function. Here, when we injected a similar dose of hydrocortisone in the afternoon, at the time of the circadian trough, we observed positive effects of GC on memory function. The results of these two studies provide evidence that GC are necessary for learning and memory in human populations.
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