The original version of the TSST, i.e. mock job interview plus mental arithmetic tasks in front of a real panel of judges, was highly effective in eliciting a stress re- sponse in every participant. Social evaluative threat and uncontrollability have been shown to be the major characteristics of the TSST explaining its effectiveness (25). Subjective reporting of disturbed mood in response to the TSST procedure suggested that all participants became personally involved in the task and found it to be highly stressful and disturbing. Notably, the majority of patients experienced the TSST as an overwhelming procedure which quite often resulted in outbreaks of emotional reac- tions such as anger, crying, sorrow or aggressive behavior. However, patients were able to complete the testing despite severe emotional reactions. One might argue whether a laboratory stressor consisting of these two essential elements, social evalu- ation and uncontrollability, is a proper reflection of the actual distress that patients face in their daily lives. Most of the time, they can use more avoidant stressregulation strategies to control the situation they face. On the other hand, in many naturalistic situations social evaluative threat and uncontrollability are strongly interconnected. For example, the behavior of the interaction partner in many situations cannot always be predicted. Also, in order to study HPA axis reactivity properly, a robust stressor is needed to evoke reliably significant elevations of free unbound cortisol.
In our collaborative effort with the NICHD Study of Early Child Care and Youth Development (SECCYD) to identify potential attachment genes, we found no evidence for additive effects of candidate genes putatively involved in attachment security and disorganization. Furthermore, proposed risk models for DRD4, DRD2, and 5-HTT failed to provide unequivocal results. However, a co-dominant effect of the COMT Val/Met proved replicable across both studies. In carriers of the heterozygous Val/Met genotype, disorganization scores were higher compared to both Val/Val and Met/Met carriers. Investigating the additional effect of maternal care on attachment quality, we found that genetic variation in the mineralocorticoid receptor gene (MR), which is involved in HPA- axis functioning, modulated infants’ sensitivity to care. Infants carrying the minor allele of MR were more securely attached if their mothers showed more sensitive responsiveness, and less securely attached if their mothers showed more extremely insensitive behaviors, whereas these associations were not significant for carriers of the wildtype genotype of MR. The findings presented in this thesis provide attachment researchers with comprehensive results on vulnerability and plasticity factors in infant attachment and stressregulation. Moreover, the findings replicate and extend previous studies by making use of data from a large attachment cohort with physiological and genetic information.
Attachment behaviors play a critical role in regulating emotion within the context of close relationships, and attachment theory is currently used to inform evidence-based practice in the areas of adolescent health and social care. This study investigated the association between female adolescents’ interview-based attachment behaviors and two markers of hypothalamic-pituitary-adrenal (HPA) axis activity: cortisol and dehydroepiandrosterone (DHEA). Unlike the classic stress hormone cortisol, there is very limited investigation of DHEA— a quintessential developmental hormone—in relation to attachment, especially in adolescents. Fifty-five healthy females mean age 14.36 (± 2.41) years participated in the Attachment Style Interview. A smaller cortisol awakening response was related to anxious attachment attitudes, including more fear of rejection, whereas greater morning basal DHEA secretion was only predicted by lower levels of reported confiding in one’s mother. These attachment-hormone relationships may be developmental markers in females, as they were independent of menarche status. These findings highlight that the normative shifts occurring in attachment to caregivers around adolescence are reflected in adolescents' biological stressregulation. We discuss how studying these shifts can be informed by
After developing a valid and reliable new questionnaire (the Cognitive Emotion Regulation Questionnaire (CERQ)), to measure cognitive emotion regulation strategies after the experience of negative life stress or trauma, results of studies in various clinical, at risk and general population samples have shown that cognitive emotion regulation strategies play an important role in the relationship between the experience of negative life stress or trauma and the reporting of symptoms of psychopathology. In order to extend these findings new
The pulsatile secretion of cortisol does, of course, raise the issue of a ‘‘pulse generator’’. In the classic LH system, the pulse generator has been localized to the arcuate nucleus by the use of multiunit electrical recording. Unfortunately, there has been very little investigation of the putative generator which could reg- ulate the activity of the HPA axis, despite the demon- stration of its ultradian as well as its circadian rhythms. It is interesting that both LH and cortisol pulses have frequencies in the 60–90 min range (circho- ral) but this does not imply a common generator, since cortisol pulses and LH pulses are not concordant (Young et al., unpublished data). While the suprachias- matic nucleus is ultimately the source of the circadian rhythm and synchronization with day night cycles, it is unclear whether it is the paraventricular nucleus of the hypothalamus itself (the location of CRF neuron cell bodies) that is the site of the rhythmic activity of the HPA axis. A recent report has suggested intrinsic rhyth- micity of the PVN in vitro , and clearly further re- search needs to be performed to shed light on this issue. Other possible hormonal inﬂuences include phase of the pulse and varying degrees of glucocorticoid negative feedback. In the rat we ﬁnd that following each peak of corticosterone secretion, there is a refractory period dur- ing which the HPA axis is resistant to activation by stressors (Figs. 2B–D) . Thus the timing of a stressor relative to the endogenous HPA pulse cycle likely plays a role in determining the size of the resultant stress re- sponse in animal models. It has been much more diﬃcult to investigate such a mechanism in man as we lack short acting, mild stressors that can be used to reproducibly increase HPA activity. In an initial exploration of this is- sue, we examined the pattern of cortisol secretion for the hour prior to administration of the TSST in 52 subjects. We subdivided the subjects into groups whose cortisol proﬁle prior to stressor exposure was increasing, decreasing, or ﬂat. The mean cortisol responses were
As one of the major branches of the stress response system, the HPA axis, whose activity is typically measured through salivary cortisol in humans, prepares the organism to respond to sustained psychological and/or physical threat by modulat- ing metabolic, immune, and cognitive functions (McEwen, 2007; Sapolsky, Romero, & Munck, 2000). A well-regulated HPA response plays a vital role in psychobiological adapta- tion to stress, and there is ample evidence that variations in HPA reactivity and recovery act as a mechanism linking ad- versity exposure with poor mental and physical health out- comes (e.g., Gunnar & Vazquez, 2001; Koss et al., 2013; Lopez-Duran, Kovacs, & George, 2009; Sturge-Apple, Da- vies, Martin, Cicchetti, & Hentges, 2012). However, there is ongoing disagreement about the type of HPA response that signals risk; whereas many of these studies point to ele- vated and/or extended cortisol responses (stress “sensitiza- tion”) among children raised in adverse environments who go on to show behavioral problems, others point to blunted responses to psychosocial stress. The differences may have to do with the intensity and/or timing of exposure, with re- searchers proposing that particularly intense chronic stress early in development can give rise to initial HPA hyperactiva- tion followed by downregulation (see Doom, Cicchetti, & Rogosch, 2014). At this point, it is important to note that reg- ulation can be defined in different ways. Here, we acknowl- edge that a variety of stress response profiles may emerge
compromised as a result of psychological or organic stress, leading to increased intestinal permeability and subsequent translocation of gram-negative bacteria across the mucosal lining to access immune cells and the ENS . Bacterial translocation leads to activation of an immune response characterised by increased production of inflammatory mediators such as IL-6 and IFNγ. In mice, pre-treatment with the probiotic L. farciminis attenuates the ability of acute restraint stress to increase intestinal permeability and HPA axis responsivity . In further support of the “leaky gut” hypothesis, serum concentrations of IgM and IgA against LPS of enterobacteria is significantly higher in MDD patients compared to healthy controls . This would suggest that bacterial translocation from the gut is increased in MDD, and the resulting inflammatory response may contribute to the mood disorder. Currently, however, clinical evidence linking MDD with alterations in the gut microbiota is relatively sparse. Naseribafrouei and colleagues failed to identify any differences in terms of microbial diversity within faecal samples obtained from MDD patients and controls, although the levels of Bacteroidetes were lower in MDD patients . Conversely, Jiang and
A substantial fraction of studies explores whether high levels of acute and chronic stress increases animals’ risk of anxiety-like behaviors or of developing a pathological aversion to novel situations; we treat those two outcomes as relevant to self-regulation because they can be considered a manifestation of emotional or behavioral dysregulation. One way of measuring these outcomes is by placing animals in conditions to which they are poorly adapted, and systematically measuring their reactions. For example, the “elevated plus maze” is a tool that takes advantage of the fact that rodents are naturally averse to open spaces and to heights; it is a structure shaped like a “+” sign, placed a few feet off the ground, on which two arms have cliff-edges and two are enclosed by high walls. In order to measure in rodents something that is akin to anxiety, researchers will place an animal in the center of one of these structures, and keep track of the amount of time it spends exploring the sections that have cliff-edges, before retreating to the more comfortable enclosed sections. Rodents who retreat very quickly are identified as experiencing a higher degree of anxiety. Other common procedures to measure anxiety or aversion to novelty include giving young primates a maternal effigy (an inanimate object that is shaped and smells like their mother) to which they can retreat and then tracking how often they retreat to it, or placing rodents on a wide, brightly lit floor and keeping track of the amount of time they spend
Poverty is a specific environmental factor with a wellestablished link to selfregulation development , which likely exerts influence on children through the chronic pressure present in families, schools, and communities. One proposed mechanism of this link is the “psychology of scarcity,” which suggests that a lack of money, food, time, or even companionship may reduce one’s “mental bandwidth” or ability to focus, plan, and problemsolve . The stress, fatigue, and worries that can accompany living in poverty reduce the energy and resources available for selfregulation and coregulation. Evidence of this effect from natural and laboratory experiments  suggests that individuals who appear to struggle with selfregulation under conditions of scarcity (e.g., living in poverty) may be just as capable as others when they have more wealth . Poverty also appears to account for some of the few differences that have been found in selfregulation among children from minority backgrounds. Specifically, although some studies  have suggested delays in inhibitory control and cognitive flexibility in AfricanAmerican and Hispanic preschoolers, controlling for poverty appears to account for these differences .
To obtain an accurate balance in stress and developmental responses, expression of WRKYs and their downstream activation is tightly regulated. For activation of certain WRKYs under biotic stress, ETI (Effector-triggered immunity) mediated regulation is required. HvWRKY1/2 are activated when fungal avirulence AVR10 effector is recognized by resistance protein MLA (mildew-resistance locus A) in the cytoplasm and the subsequent association of MLA with the WRKYs in the nucleus ( Shen et al., 2007 ). Nicotiana attenuate NaWRKY3 is required for NaWRKY6 activation by fatty acid–amino conjugates found in the oral secretions of Manducasexta larva. After wounding mediated activation they process responses to herbivory ( Skibbe et al., 2008 ). In another case of herbivory, Spodoptera littoralis induces the synthesis of JA-isoleucine that binds to a complex of receptor COI1 and repressor JAZ finally activating AtWRKY18 and AtWRKY40 ( Schweizer et al., 2013 ). Similarly AtWRKY23 is upregulated upon Heterodera schachtii nematode infection ( Grunewald et al., 2008 ). OsBWMK1 phosphorylates OsWRKY33, which binds to the W box element present in the promoter of several PR genes ( Koo et al., 2009 ). PAD4, a key regulator of SA signaling regulates AtWRKY33 which provides resistance to B. cinerea and regulates genes involved in redox homeostasis, SA signaling, ET-JA-mediated cross- communication and camalexin biosynthesis ( Qiu et al., 2008 ). BHLH and R2R3MYB TFs (WEREWOLF, GLABRA1, and TRANSPARENT TESTA) regulate the expression of TTG2 that plays a role in trichome and seed development by regulating expression of GLABRA2 ( Ishida et al., 2007 ). TTG2 also increases sensitivity to salt stress through suppression of auxin biosynthetic genes ( Li Q. et al., 2015 ). Zinc-finger protein Zat12 is induced by drought, osmotic, salinity, temperature, oxidative stress, and wounding which in turn transcriptionally regulates
levels. Abiotic stress potentially affects the structure and properties of preformed and inducible physical barriers that function against pathogen penetration. Signaling nodes such as RBOHs and RLKs and other cell wall (CW) kinases localized at the plasma membrane, and MAPKs are shared by both stressors, with downstream signal specificity under stress combination remaining elusive. ABA signaling, central for adaptation to abiotic stress, negatively impinges on defense hormone signaling, while, pathogen dependent, positive interactions are observed for JA signaling. ABA-SA interaction is two sided, as activation of SA signaling by pathogen challenge attenuates ABA responses. ABA positively contributes to pre-invasion defense, enhancing callose deposition. Rewiring of secretory machinery under abiotic stress potentially affects its function in the exocytosis of antimicrobial compounds at the site of infection. Nuclear translocation of R-genes is negatively affected under abiotic stress. Redox state, as well as metabolite concentration such as sugars and amino acids (AA), function as drivers for post-translational modifications, modulating the activity of target proteins/transcription factors. Previously/simultaneously encountered stress effect on chromatin and DNA methylation status, potentially impacts on expression patterns of the recipient genes under stress combination. Transcription factor activation and binding to stress responsive gene promoters is a convergence point regulating the signal output under combinatorial stress with diverse outcomes.
The ART programme is an intensive six week training regimen, which requires practice of the whole ART sequence for approximately 20-30 minutes per day. Furthermore, in their own time clients are required to engage in at least three exercises lasting from three seconds to three minutes. Clients also receive homework, handouts, an information booklet, audio files and 140 text messages to prompt activity or provide information during the training (Berking & Whitley, 2014). The ART structure of specific skill focused modules contrasts with the other primarily emotion regulation based intervention, Emotion Regulation Therapy (ERT; Mennin & Fresco, 2014). ERT was designed as an addition to a normal CBT programme for comorbid depression and anxiety. In addition to completing a CBT course, ERT clients attend extra sessions to cover: the motivational mechanisms behind behaviour; different regulation methods and their emotional consequences in context. Both of these treatments are relatively intensive and train a variety of emotion regulation strategies during these sessions, where this study aims to teach exclusively on catastrophising and its prevention. Therefore, a low intensity approach would better fit the requirements for this intervention than the structures applied by current emotion regulation treatments. Conceptually, this study is investigating at the scale of a module rather than a fully rounded intervention.
Self-regulation serves as the foundation for lifelong functioning across a wide range of domains, from mental health and emotional wellbeing to academic achievement, physical health, and socio- economic success. It has also proven responsive to intervention, making it a powerful target for change.
Chondrogenesis and endochondral ossification are the cartilage differentiation processes that lead to skeletal formation and growth in the developing vertebrate as well as skeletal repair in the adult. The exquisite regulation of these processes, both in normal development and in pathologic situations, is impacted by a number of different types of stress. These include normal stressors such as mechanical loading and hypoxia as well pathologic
tury disease and World Health Organization reported it as an epidemic problem . Stress is an affective, cognitive, behavioral and mental reaction to harmful aspects of work and workplace  . Generally, job stress can be considered as a response to work-related pressures that happens when expectation from someone is beyond his capability and authorization  . In this respect, our findings indicated that there is a significant relationship between life orientation and job stress. In other words, optimist employees with positive life orientation have the lowest job stress. In fact, a positive view towards life will lead to de- crease in daily stress which significantly will decrease job stresses too. When coping with daily problems and even job related problems, employees with rea- sonable and positive attitude towards life have the lowest stress level due to their optimist thoughts.
Mental arithmetic leads changes of the cortical potential, part of which are related to neural and cardiovascular response . The neurocardiology, which focuses on anat- omy and function connection between heart and brain, represents the intersection of neurology and cardiology [11, 12]. These brain–heart interactions help to explain the apparent randomness of sudden cardiac events and provide new insights into future novel therapies to prevent sudden death. Previous studies have given description about regulation of heart by ANS. This mechanism involves amygdala, insular cortex, parabra- chial complex, hypothalamus, periaqueductal gray matter, nucleus of the tractus solitar- ius, and ventrolateral medulla [13–15]. In fact, the connection of heart and brain may be different within stresses. The toxic effects of mental stress on cardiovascular function remind us to focus on the specific mechanism about how cortex activity dynamically regulates ANS, which is still beyond present study.
The first information on trans-regulators of Yap1p localiza- tion came from studies on the function of the exportin Crm1p. Crm1p was first identified in S. pombe as a factor required for normal chromatin structure (1). Mutant forms of Crm1p were noted to confer staurosporine resistance and to overproduce a protein of 25 kDa. Strikingly, overexpression of the pap1⫹ gene, encoding the S. pombe Yap1p homologue, also produced these same phenotypes (84). Genetic analyses indicated that Crm1p negatively regulated Pap1 function. Later work on Crm1p in S. cerevisiae demonstrated that this exportin was involved in control of Yap1p nuclear localization (47, 95). Use of a temperature-sensitive form of Crm1p led to trapping of Yap1p in the nuclei of cells shifted to the restrictive temper- ature. In vitro and in vivo experiments argued that Yap1p and Crm1p interacted in an oxidant-sensitive fashion; increasing the level of oxidant decreased the degree of interaction. Sub- stitution mutations in the c-CRD cysteine residues led to con- stitutive elimination of Yap1p-Crm1p interactions. Study of the nuclear import of Yap1p failed to find an oxidant-regulated step in the entry of Yap1p to the nucleus (35). These obser- vations led to the model that Yap1p localization control was provided by regulation of the nuclear export of this protein. In nonstressed cells, Yap1p enters the nucleus, interacts with Crm1p, and is rapidly returned to the cytoplasm. However, in oxidant-challenged cells, Yap1p-Crm1p interaction is dis- turbed via modification of the c-CRD, Yap1p accumulates in the nucleus, and target genes containing a Yap1p response element are upregulated. In the case of an oxidant like diam- ide, most of the information conferring regulation of Yap1p localization is present in the c-CRD region of the factor.
The roles of Hsf1 target genes other than HSP104 in ther- motolerance remained obscure. In investigations using an hsf1 mutation named hsf1-m3, it has been reported that high-level induction of Hsps is not required for the acquisition of ther- motolerance (42). Later analysis showed that Hsp104 expres- sion is sufficient for thermotolerance (25). Our results show that cells containing the hsf1-R206S-H220R mutation are more sensitive to severe heat shock than wild-type cells, even though HSP104 is constitutively expressed, and that target genes other than HSP104 appear to be involved in the thermotolerance mediated by Hsf1. Thermotolerance can be considered to be the result of both increased protection of cellular components at extreme temperatures and increased reactivation and/or degradation of heat-inactivated components (Fig. 5). Genetic analysis has shown that, in the absence of Hsp104, the Hsp70 family is very important for thermotolerance (36). In mito- chondria, a set of chaperones is crucial for the maintenance of respiratory competence and mitochondrial DNA synthesis (10, 38). These results suggest that Hsf1-mediated expression of various Hsps is needed to protect proteins against thermal inactivation and aggregation. In addition to HSP genes, Hsf1 regulates the transcription of genes involved in ubiquitination and proteolysis (17, 51). Furthermore, RPN4 encodes a tran- scriptional activator of genes coding for proteasome subunits, FIG. 5. Schematic representation of regulation of thermotolerance by Hsf1 and Msn2/4. Cells acquire thermotolerance upon mild heat shock, during which Hsf1 and Msn2/4 induce expression of proteins involved in protection of cellular components against heat inactivation. In severely heat-shocked cells, promoter-bound, hyperphosphorylated Hsf1 is unable to activate transcription because RNA polymerase II (RNAPII) is inactive. It is unknown whether the transcriptional activ- ity of Msn2/4 is activated by severe heat shock. In recovering cells, misfolded proteins appear to activate Hsf1, which induces expression of proteins involved in reactivation and/or degradation of heat-inacti- vated components. The transcriptional activity of Msn2/4 is not subject to delayed upregulation. More details are described in the text.