Biomarking Trait Resilience With Salivary Cortisol in Chinese Undergraduates.

This study aimed to examine the relationship between trait resilience and salivary cortisol in a group of Chinese undergraduates. The Chinese versions of the Brief Resilience Scale and a measure of optimism, the revised Life Orientation Test were administered to 49 Chinese undergraduates who provided self-collected saliva samples six times per day (immediately after waking; 0.5, 3, 6, and 12 h thereafter; and at bedtime) over 3 consecutive weekdays. The cortisol data were aggregated across the 3 days to examine the association between resilience and components of the diurnal rhythm of cortisol using multiple regression. The results showed that higher resilience was associated with a stronger cortisol response to awakening and a steeper diurnal decline in cortisol from waking to bedtime. Resilience was positively associated with cortisol output over the course of the day but this relationship was not significant (p = 0.065). This pattern of diurnal rhythm is consistent with that typically observed in better adjusted individuals. Generated by an intensive protocol with compliance objectively monitored, these findings clearly indicate the important role of the hypothalamic-pituitary-adrenocortical axis in health and adjustment and contribute to the growing literature on resilience and cortisol in humans.

Daily hassles, loneliness, and diurnal salivary cortisol in emerging adults.

This study used an intensive protocol to examine the effects of daily hassles and loneliness on diurnal salivary cortisol levels. Fifty Chinese undergraduates (28 females) provided six saliva samples each day for two consecutive days (at 0, 0.5, 3, 6, and 12 h after waking and at bedtime) and completed a questionnaire that included scales to measure daily hassles experienced over the previous month, trait loneliness, and depression. Cortisol data were aggregated over two days and used in subsequent analyses, focusing on the cortisol awakening response, diurnal slope, and overall cortisol output operationalized as the area under the curve with reference to the ground (AUCG). Multiple regression analysis showed that an increase in loneliness had a significant association with an increase in the AUCG and with a steeper diurnal slope. Loneliness also showed a significant interaction with daily hassles in that the positive association between daily hassles and AUCG was accentuated in the participants who reported a greater degree of loneliness. Our findings demonstrate for the first time the importance of trait loneliness in modulating the association between daily hassles and diurnal cortisol levels, which has significant clinical implications. Interventions to reduce loneliness should help college students to better cope with daily stressors. Increased attention should also be paid to the health implications of an elevated cortisol level in this relatively young and healthy population.

Network cultivation, diurnal cortisol and biological ageing: The rejuvenation hypothesis.

A stronger motivation to cultivate social ties in older adults (ages range from 62 to 86 years) has been associated with a cortisol profile similar to that observed in undergraduate students, who are decades younger. We have shown the cultivation of social networks buffers against increases in diurnal cortisol common in old age. Cortisol is crucial for the response to stress and the process of ageing, and a recent study has demonstrated that a lower cortisol level is associated with longevity. We link the findings of social network cultivation and cortisol profile to the processes of biological ageing through DNA telomere length. Telomeres are repeated DNA sequences that cap and protect the ends of chromosomes, and telomere length is considered a potential biomarker for biological age because it is closely related to the cellular process of ageing and chronic stress and is inversely related to chronological age. Studies examining biological ageing have shown an association between an altered cortisol profile and telomere length dynamics. Together, these findings on social networks, cortisol profiles and telomere length suggest that seniors who are motivated to maintain social ties are biologically younger. We therefore propose the 'rejuvenation hypothesis', which posits that seniors with a stronger motivation for social network cultivation are biologically younger, as measured by cortisol levels and telomere length, than their peers who are less motivated to pursue social relationships. This idea suggests a new perspective and potentially fruitful direction for geriatric research. The focus on social network cultivation adds an important psychosocial dimension to rejuvenation therapies that so far have been dominated by biomedical approaches. The rejuvenation hypothesis also has important implications for social policy by supporting the viability of promoting network cultivation among the elderly to facilitate healthy ageing.

Loneliness and Diurnal Salivary Cortisol in Emerging Adults.

This study aimed to examine the relationship between trait loneliness and diurnal rhythms of salivary cortisol. Fifty-One Chinese undergraduates provided six saliva samples on a weekday at immediately, 0.5, 3, 6, and 12 h after waking, and at bedtime. Saliva collection times were monitored using electronic devices (MEMS TrackCaps). Participants were also administered a questionnaire consisting of scales measuring, trait loneliness, depression, and demographics. Relationships between loneliness and the cortisol awakening response (CAR), diurnal slope (DS), and area under the curve with respect to ground (AUCG) were examined using multiple regression analyses. Results showed that a higher loneliness score was associated with an attenuated CAR, a large AUCG, and a steeper DS, with the effects of compliance, waking time, and depression being controlled. As a blunted CAR and a higher diurnal cortisol level have been shown to be associated with poorer health in prior studies, increased attention to the mechanisms translating loneliness into disease endpoints via elevated cortisol is warranted.

Increasing the accuracy and scalability of the Immunofluorescence Assay for Epstein Barr Virus by inferring continuous titers from a single sample dilution.

High Epstein Barr Virus (EBV) titers detected by the indirect Immunofluorescence Assay (IFA) are a reliable predictor of Nasopharyngeal Carcinoma (NPC). Despite being the gold standard for serological detection of NPC, the IFA is limited by scaling bottlenecks. Specifically, 5 serial dilutions of each patient sample must be prepared and visually matched by an evaluator to one of 5 discrete titers. Here, we describe a simple method for inferring continuous EBV titers from IFA images acquired from NPC-positive patient sera using only a single sample dilution. In the first part of our study, 2 blinded evaluators used a set of reference titer standards to perform independent re-evaluations of historical samples with known titers. Besides exhibiting high inter-evaluator agreement, both evaluators were also in high concordance with historical titers, thus validating the accuracy of the reference titer standards. In the second part of the study, the reference titer standards were IFA-processed and assigned an 'EBV Score' using image analysis. A log-linear relationship between titers and EBV Score was observed. This relationship was preserved even when images were acquired and analyzed 3days post-IFA. We conclude that image analysis of IFA-processed samples can be used to infer a continuous EBV titer with just a single dilution of NPC-positive patient sera. This work opens new possibilities for improving the accuracy and scalability of IFA in the context of clinical screening.

Short photoperiod condition increases susceptibility to stress in adolescent male rats.

The seasonality of depressive symptoms is prevalent in children and adolescents. However, the mechanisms that underlie such susceptibility to seasonal influences on mood disorders are unclear. We examined the effects of a short photoperiod condition on the susceptibility to subchronic unpredictable mild stress (SCUS) and rhythmic alterations of plasma corticosterone (CORT), melatonin, and neuropeptide Y (NPY) in adolescent male rats. Compared with the 12h/12h light/dark photoperiod control (CON) rats, the 8h/16h photoperiod SCUS rats exhibited significant anhedonia, a core symptom of human depression, together with a blunted diurnal rhythm and elevation of 24h CORT, melatonin, and NPY levels. The 8h/16h photoperiod condition also blunted the rhythmicity of CORT, caused a phase inversion of melatonin, and caused a phase delay of NPY compared with 12h/12h CON rats. Such abnormalities of plasma CORT, NPY, and melatonin might cause adolescent individuals to present higher stress reactivity and greater vulnerability to stress over their lifetimes. The present study provides evidence of the susceptibility to the seasonality of stress-related disorders in adolescence.

Cellular Subcompartments through Cytoplasmic Streaming.

Cytoplasmic streaming occurs in diverse cell types, where it generally serves a transport function. Here, we examine streaming in multicellular fungal hyphae and identify an additional function wherein regimented streaming forms distinct cytoplasmic subcompartments. In the hypha, cytoplasm flows directionally from cell to cell through septal pores. Using live-cell imaging and computer simulations, we identify a flow pattern that produces vortices (eddies) on the upstream side of the septum. Nuclei can be immobilized in these microfluidic eddies, where they form multinucleate aggregates and accumulate foci of the HDA-2 histone deacetylase-associated factor, SPA-19. Pores experiencing flow degenerate in the absence of SPA-19, suggesting that eddy-trapped nuclei function to reinforce the septum. Together, our data show that eddies comprise a subcellular niche favoring nuclear differentiation and that subcompartments can be self-organized as a consequence of regimented cytoplasmic streaming.

Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity.

Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity.

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial.

BACKGROUND: Caregivers of relatives with Alzheimer's disease are highly stressed and at risk for physical and psychiatric conditions. Interventions are usually focused on providing caregivers with knowledge of dementia, skills, and/or support, to help them cope with the stress. This model, though true to a certain extent, ignores how caregiver stress is construed in the first place. Besides burden, caregivers also report rewards, uplifts, and gains, such as a sense of purpose and personal growth. Finding benefits through positive reappraisal may offset the effect of caregiving on caregiver outcomes. DESIGN: Two randomized controlled trials are planned. They are essentially the same except that Trial 1 is a cluster trial (that is, randomization based on groups of participants) whereas in Trial 2, randomization is based on individuals. Participants are randomized into three groups - benefit finding, psychoeducation, and simplified psychoeducation. Participants in each group receive a total of approximately 12 hours of training either in group or individually at home. Booster sessions are provided at around 14 months after the initial treatment. The primary outcomes are caregiver stress (subjective burden, role overload, and cortisol), perceived benefits, subjective health, psychological well-being, and depression. The secondary outcomes are caregiver coping, and behavioral problems and functional impairment of the care-recipient. Outcome measures are obtained at baseline, post-treatment (2 months), and 6, 12, 18 and 30 months. DISCUSSION: The emphasis on benefits, rather than losses and difficulties, provides a new dimension to the way interventions for caregivers can be conceptualized and delivered. By focusing on the positive, caregivers may be empowered to sustain caregiving efforts in the long term despite the day-to-day challenges. The two parallel trials will provide an assessment of whether the effectiveness of the intervention depends on the mode of delivery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org/en/) identifier number ChiCTR-TRC-10000881.

Social network characteristics and salivary cortisol in healthy older people.

Psychobiological research on aging in humans has been confounded by individual differences that have not been adequately characterized in the literature. This paper is an attempt to shed light on this issue by examining the impact of social network characteristics predictive of successful aging on salivary cortisol among 78 older Chinese people in Hong Kong. Eight salivary cortisol samples were collected each day for two consecutive days from immediately after awakening to 12 hours later. Two components of the cortisol diurnal cycle, response to awakening and diurnal decline, were examined in relation to social network characteristics including size, emotional support, and cultivation. ANOVAs with repeated measured were run to examine influences of the three social network characteristics on the cortisol awakening response and diurnal decline, with the effects of gender, age, socioeconomic status, and waking time controlled. Results indicated that those who spent more time and effort in developing and strengthening their social ties (i.e., those high in "cultivation") exhibited a significantly greater rise in cortisol in the morning and a significantly steeper decline over the day, thus attesting to more effective activation and deactivation of the HPA axis. Network cultivation reflected a positive motivation to nurture social relationships more than the other two network characteristics. Its effect on cortisol might stem from the positivity underlying the motivation.

Humor attenuates the cortisol awakening response in healthy older men.

This study examined the impact of an important factor contributing to successful aging, humor, on post-awakening cortisol levels among a group of 45 older men whose ages ranged from 64 years to 86 years (mean=73.6 years). Four saliva samples were collected from the participants for 2 days immediately after waking and every 15 min thereafter for three times. Cortisol data of the 2 days were aggregated for analysis. Two separate indices of cortisol awakening response reflecting the mean level of secretion and the rise from immediately to 45 min post-awakening, AUC(G) and AUC(I), were computed using the trapezoid formula. The relation of these two indices to humor (operationalized as coping) was examined in a multiple regression analysis while controlling for the effect of age, socioeconomic status, and self-esteem. Results indicated that higher humor scores were associated with lower AUC(G) but had no relation with AUC(I). Findings of the present study suggest that the hypothalamic-pituitary-adrenocortical axis is the major pathway whereby positive psychological dispositions, such as humor, exert their health effects in the aging population. Moreover, cortisol levels in the awakening period may be particularly sensitive to the influences of psychosocial factors.

Marker fusion tagging, a new method for production of chromosomally encoded fusion proteins.

A new gene-tagging method (marker fusion tagging [MFT]) is demonstrated for Neurospora crassa and Magnaporthe oryzae. Translational fusions between the hygromycin B resistance gene and various markers are inserted into genes of interest by homologous recombination to produce chromosomally encoded fusion proteins. This method can produce tags at any position and create deletion alleles that maintain N- and C-terminal sequences. We show the utility of MFT by producing enhanced green fluorescent protein (EGFP) tags in proteins localized to nuclei, spindle pole bodies, septal pore plugs, Woronin bodies, developing septa, and the endoplasmic reticulum.

A tether for Woronin body inheritance is associated with evolutionary variation in organelle positioning.

Eukaryotic organelles evolve to support the lifestyle of evolutionarily related organisms. In the fungi, filamentous Ascomycetes possess dense-core organelles called Woronin bodies (WBs). These organelles originate from peroxisomes and perform an adaptive function to seal septal pores in response to cellular wounding. Here, we identify Leashin, an organellar tether required for WB inheritance, and associate it with evolutionary variation in the subcellular pattern of WB distribution. In Neurospora, the leashin (lah) locus encodes two related adjacent genes. N-terminal sequences of LAH-1 bind WBs via the WB-specific membrane protein WSC, and C-terminal sequences are required for WB inheritance by cell cortex association. LAH-2 is localized to the hyphal apex and septal pore rim and plays a role in colonial growth. In most species, WBs are tethered directly to the pore rim, however, Neurospora and relatives have evolved a delocalized pattern of cortex association. Using a new method for the construction of chromosomally encoded fusion proteins, marker fusion tagging (MFT), we show that a LAH-1/LAH-2 fusion can reproduce the ancestral pattern in Neurospora. Our results identify the link between the WB and cell cortex and suggest that splitting of leashin played a key role in the adaptive evolution of organelle localization.

Making two organelles from one: Woronin body biogenesis by peroxisomal protein sorting.

Woronin bodies (WBs) are dense-core organelles that are found exclusively in filamentous fungi and that seal the septal pore in response to wounding. These organelles consist of a membrane-bound protein matrix comprised of the HEX protein and, although they form from peroxisomes, their biogenesis is poorly understood. In Neurospora crassa, we identify Woronin sorting complex (WSC), a PMP22/MPV17-related membrane protein with dual functions in WB biogenesis. WSC localizes to large peroxisome membranes where it self-assembles into detergent-resistant oligomers that envelop HEX assemblies, producing asymmetrical nascent WBs. In a reaction requiring WSC, these structures are delivered to the cell cortex, which permits partitioning of the nascent WB and WB inheritance. Our findings suggest that WSC and HEX collaborate and control distinct aspects of WB biogenesis and that cortical association depends on WSC, which in turn depends on HEX. This dependency helps order events across the organellar membrane, permitting the peroxisome to produce a second organelle with a distinct composition and intracellular distribution.

Optimism, positive affectivity, and salivary cortisol.

OBJECTIVES: Research on stress and salivary cortisol has focused almost exclusively on the effects of negative psychological conditions or emotional states. Little attention has been drawn to the impact associated with positive psychological conditions, which have been shown recently to have significant influences on neuroendocrine regulation. The aim of this study is to examine the impact of optimism and positive affect on salivary cortisol with the effects of their negative counterparts controlled for. DESIGN: Optimism and pessimism, and positive and negative affectivity were studied in relation to the diurnal rhythm of salivary cortisol in a group of 80 Hong Kong Chinese, who provided six saliva samples over the course of a day on two consecutive days. The separate effects of optimism and positive affect on two dynamic components of cortisol secretion, awakening response, and diurnal decline were examined. METHODS: Optimism and pessimism were measured using the Chinese version of the revised Life Orientation Test while generalized affects and mood states were assessed by the Chinese Affect Scale. An enzyme-linked immunoabsorbent assay kit (EIA) developed for use in saliva was adopted for the biochemical analysis of cortisol. Testing of major group differences associated with positive psychological conditions was carried out using two-way (group by saliva collection time) ANOVAs for repeated measures with negative psychological conditions and mood states as covariates. RESULTS: Participants having higher optimism scores exhibited less cortisol secretion in the awakening period when the effect of pessimism and mood were controlled. This effect was more apparent in men than in women who had higher cortisol levels in the awakening period. Optimism did not have similar effect on cortisol levels during the underlying period of diurnal decline. On the other hand, higher generalized positive affect was associated with lower cortisol levels during the underlying period of diurnal decline after the effects of negative affect and mood states had been controlled. Generalized positive affect did not significantly influence cortisol secretion during the awakening period. CONCLUSIONS: These findings suggest that positive psychological resources including optimism and generalized positive affect had higher impact on cortisol secretion than their negative counterparts, and point to the need for increased attention to the potential contribution of positive mental states to well-being.

Perception of environmental hazards in Hong Kong Chinese.

A public sample of Hong Kong Chinese (N = 167) rated the levels of threat of 25 environmental hazards and gave quantitative judgments to six risk characteristics for each hazard. It was found that women, older participants, and less educated individuals found the hazards to be more threatening to the environment than did men, younger participants, and more educated individuals, respectively. A new spatial model emerged from a principal component analysis carried out on responses to six risk characteristics. Instead of replicating the well-documented factors of unknown risk versus dread risk, we found a structure defined by a known and dread risk factor and a controllable risk factor. Findings were discussed in light of potential influences of the Confucian heritage on the perception of risks among Hong Kong Chinese.