Born to yawn? Understanding yawning as a warning of the rise in cortisol levels: Randomized trial

Background: Yawning consistently poses a conundrum to the medical profession and neuroscientists. Despite neurological evidence such as parakinesia brachialis oscitans in stroke patients and thermo-irregulation in multiple sclerosis patients, there is considerable debate over the reasons for yawning with the mechanisms and hormonal pathways still not fully understood. Cortisol is implicated during yawning and may link many neurological disorders. Evidence was found in support of the Thompson cortisol hypothesis that proposes cortisol levels are elevated during yawning just as they tend to rise during stress and fatigue. Objectives: To investigate whether saliva cortisol levels rise during yawning and, therefore, support the Thompson cortisol hypothesis. Methods: We exposed 20 male and female volunteers aged between 18 and 53 years to conditions that provoked a yawning response in a randomized controlled trial. Saliva samples were collected at the start and again after the yawning response, or at the end of the stimuli presentations if the participant did not yawn. In addition, we collected electromyographic data of the jaw muscles to determine rest and yawning phases of neural activity. Yawning susceptibility scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, and demographic and health details were also collected from each participant. A comprehensive data set allowed comparison between yawners and nonyawners, as well as between rest and yawning phases. Collecting electromyographic data from the yawning phase is novel, and we hope this will provide new information about neuromuscular activity related to cortisol levels. Exclusion criteria included chronic fatigue, diabetes, fibromyalgia, heart conditions, high blood pressure, hormone replacement therapy, multiple sclerosis, and stroke. We compared data between and within participants. Results: In the yawning group, there was a significant difference between saliva cortisol samples (t = -3.071, P = .01). Power and effect size were computed based on repeated-measures t tests for both the yawning and nonyawning groups. There was a medium effect size for the nonyawners group (r = .467) but low power (36%). Results were similar for the yawners group: medium effect size (r = .440) and low power (33%). Conclusions: There was significant evidence in support of the Thompson cortisol hypothesis that suggests cortisol levels are elevated during yawning. A further longitudinal study is planned to test neurological patients. We intend to devise a diagnostic tool based on changes in cortisol levels that may assist in the early diagnosis of neurological disorders based on the data collected. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 61942768; http://www.controlled-trials.com/ISRCTN61942768/61942768 (Archived by WebCite at http://www.webcitation.org/6A75ZNYvr)

Foraging Behavior under Starvation Conditions Is Altered via Photosynthesis by the Marine Gastropod, Elysia clarki

It has been well documented that nutritional state can influence the foraging behavior of animals. However, photosynthetic animals, those capable of both heterotrophy and symbiotic photosynthesis, may have a delayed behavioral response due to their ability to photosynthesize. To test this hypothesis we subjected groups of the kleptoplastic sea slug, Elysia clarki, to a gradient of starvation treatments of 4, 8, and 12 weeks plus a satiated control. Compared to the control group, slugs starved 8 and 12 weeks displayed a significant increase in the proportion of slugs feeding and a significant decrease in photosynthetic capability, as measured in maximum quantum yield and [chl a]. The 4 week group, however, showed no significant difference in feeding behavior or in the metrics of photosynthesis compared to the control. This suggests that photosynthesis in E. clarki, thought to be linked to horizontally-transferred algal genes, delays a behavioral response to starvation. This is the first demonstration of a link between photosynthetic capability in an animal and a modification of foraging behavior under conditions of starvation

Specific Activation of Estrogen Receptor Alpha and Beta Enhances Male Sexual Behavior and Neuroplasticity in Male Japanese Quail

Two subtypes of estrogen receptors (ER), ERα and ERβ, have been identified in humans and numerous vertebrates, including the Japanese quail. We investigated in this species the specific role(s) of each receptor in the activation of male sexual behavior and the underlying estrogen-dependent neural plasticity. Castrated male Japanese quail received empty (CX) or testosterone-filled (T) implants or were daily injected with the ER general agonist diethylstilbestrol (DES), the ERα-specific agonist PPT, the ERβ-specific agonist DPN or the vehicle, propylene glycol. Three days after receiving the first treatment, subjects were alternatively tested for appetitive (rhythmic cloacal sphincter movements, RCSM) and consummatory aspects (copulatory behavior) of male sexual behavior. 24 hours after the last behavioral testing, brains were collected and analyzed for aromatase expression and vasotocinergic innervation in the medial preoptic nucleus. The expression of RCSM was activated by T and to a lesser extent by DES and PPT but not by the ERβagonist DPN. In parallel, T fully restored the complete sequence of copulation, DES was partially active and the specific activation of ERα or ERβ only resulted in a very low frequency of mount attempts in few subjects. T increased the volume of the medial preoptic nucleus as measured by the dense cluster of aromatase-immunoreactive cells and the density of the vasotocinergic innervation within this nucleus. DES had only a weak action on vasotocinergic fibers and the two specific ER agonists did not affect these neural responses. Simultaneous activation of both receptors or treatments with higher doses may be required to fully activate sexual behavior and the associated neurochemical events

The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε

Replication fork stalling and accumulation of single-stranded DNA trigger the S phase checkpoint, a signalling cascade that, in budding yeast, leads to the activation of the Rad53 kinase. Rad53 is essential in maintaining cell viability, but its targets of regulation are still partially unknown. Here we show that Rad53 drives the hyper-SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε, principally following replication forks stalling induced by nucleotide depletion. Pol2 is the main target of SUMOylation within the replisome and its modification requires the SUMO-ligase Mms21, a subunit of the Smc5/6 complex. Moreover, the Smc5/6 complex co-purifies with Pol ε, independently of other replisome components. Finally, we map Pol2 SUMOylation to a single site within the N-terminal catalytic domain and identify a SUMO-interacting motif at the C-terminus of Pol2. These data suggest that the S phase checkpoint regulate Pol ε during replication stress through Pol2 SUMOylation and SUMO-binding abilit

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease