Resilience by design: How nature, nurture, environment, and microbiome mitigate stress and allostatic load.

Resilience to psychological stress is defined as adaption to challenging life experiences and not the absence of adverse life events. Determinants of resilience include personality traits, genetic/epigenetic modifications of genes involved in the stress response, cognitive and behavioral flexibility, secure attachment with a caregiver, social and community support systems, nutrition and exercise, and alignment of circadian rhythm to the natural light/dark cycle. Therefore, resilience is a dynamic and flexible process that continually evolves by the intersection of different domains in human's life; biological, social, and psychological. The objective of this minireview is to summarize the existing knowledge about the multitude factors and molecular alterations that result from resilience to stress response. Given the multiple contributing factors in building resilience, we set out a goal to identify which factors were most supportive of a causal role by the current literature. We focused on resilience-related molecular alterations resulting from mind-body homeostasis in connection with psychosocial and environmental factors. We conclude that there is no one causal factor that differentiates a resilient person from a vulnerable one. Instead, building resilience requires an intricate network of positive experiences and a healthy lifestyle that contribute to a balanced mind-body connection. Therefore, a holistic approach must be adopted in future research on stress response to address the multiple elements that promote resilience and prevent illnesses and psychopathology related to stress allostatic load.

Light at night exacerbates metabolic dysfunction in a polygenic mouse model of type 2 diabetes mellitus.

AIMS: Electric lighting is beneficial to modern society; however, it is becoming apparent that light at night (LAN) is not without biological consequences. Several studies have reported negative effects of LAN on health and behavior in humans and nonhuman animals. Exposure of non-diabetic mice to dim LAN impairs glucose tolerance, whereas a return to dark nights (LD) reverses this impairment. We predicted that exposure to LAN would exacerbate the metabolic abnormalities in TALLYHO/JngJ (TH) mice, a polygenic model of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We exposed 7-week old male TH mice to either LD or LAN for 8-10 weeks in two separate experiments. After 8 weeks of light treatment, we conducted intraperitoneal glucose tolerance testing (ipGTT) followed by intraperitoneal insulin tolerance testing (ipITT). In Experiment 1, all mice were returned to LD for 4 weeks, and ipITT was repeated. KEY FINDINGS: The major results of this study are i) LAN exposure for 8 weeks exacerbates glucose intolerance and insulin resistance ii) the effects of LAN on insulin resistance are reversed upon return to LD, iii) LAN exposure results in a greater increase in body weight compared to LD exposure, iv) LAN increases the incidence of mice developing overt T2DM, and v) LAN exposure decreases survival of mice with T2DM. SIGNIFICANCE: In conclusion, LAN exacerbated metabolic abnormalities in a polygenic mouse model of T2DM, and these effects were reversed upon return to dark nights. The applicability of these findings to humans with T2DM needs to be determined.

Dark matters: effects of light at night on metabolism.

Life on earth has evolved during the past several billion years under relatively bright days and dark night conditions. The wide-spread adoption of electric lights during the past century exposed animals, both human and non-human, to significant light at night for the first time in their evolutionary history. Endogenous circadian clocks depend on light to entrain to the external daily environment and seasonal rhythms depend on clear nightly melatonin signals to assess time of year. Thus, light at night can derange temporal adaptations. Indeed, disruption of naturally evolved light-dark cycles results in several physiological and behavioural changes with potentially serious implications for physiology, behaviour and mood. In this review, data from night-shift workers on their elevated risk for metabolic disorders, as well as data from animal studies will be discussed. Night-shift workers are predisposed to obesity and dysregulated metabolism that may result from disrupted circadian rhythms. Although studies in human subjects are correlative, animal studies have revealed several mechanisms through which light at night may exert its effects on metabolism by disrupting circadian rhythms that are associated with inflammation, both in the brain and in the periphery. Disruption of the typical timing of food intake is a key effect of light at night and subsequent metabolic dysregulation. Strategies to avoid the effects of light at night on body mass dysregulation should be pursued.

Structural and membrane binding properties of the prickle PET domain.

The planar cell polarity (PCP) pathway is required for fetal tissue morphogenesis as well as for maintenance of adult tissues in animals as diverse as fruit flies and mice. One of the key members of this pathway is Prickle (Pk), a protein that regulates cell movement through its association with the Dishevelled (Dsh) protein. Pk presents three LIM domains and a PET domain of unknown structure and function. Both the PET and LIM domains control membrane targeting of Dsh, which is necessary for Dsh function in the PCP pathway. Here, we show that the PET domain is monomeric and presents a nonglobular conformation with some properties of intrinsically disordered proteins. The PET domain adopts a helical conformation in the presence of 2,2,2-trifluoroethanol (TFE), a solvent known to stabilize hydrogen bonds within the polypeptide backbone, as analyzed by circular dichroism (CD) and NMR spectroscopy. Furthermore, we found that the conserved and single tryptophan residue in PET, Trp 536, moves to a more hydrophobic environment when accompanied with membrane penetration and that the protein becomes more helical in the presence of lipid micelles. The presence of LIM domains, downstream of PET, increases protein folding, thermostability, and tolerance to limited proteolysis. In addition, pull-down and tryptophan fluorescence analyses suggest that the LIM domains physically interact to regulate membrane penetration of the PET domain. The findings reported here favor a model where the PET domain is engaged in Pk membrane insertion, whereas the LIM domains modulate this function.