Isolation of an immunodominant viral peptide that is endogenously bound to the stress protein GP96/GRP94.

Heat shock protein gp96 primes class I restricted cytotoxic T cells against antigens present in the cells from which it was isolated. Moreover, gp96 derived from certain tumors functions as an effective vaccine, causing complete tumor regressions in in vivo tumor challenge protocols. Because tumor-derived gp96 did not differ from gp96 isolated from normal tissues, a role for gp96 as a peptide carrier has been proposed. To test this hypothesis, we analyzed whether such an association of antigenic peptides with gp96 occurs in a well-defined viral model system. Here we present the full characterization of an antigenic peptide that endogenously associates with the stress protein gp96 in cells infected with vesicular stomatitis virus (VSV). This peptide is identical to the immunodominant peptide of VSV, which is also naturally presented by H-2Kb major histocompatibility complex class I molecules. This peptide associates with gp96 in VSV-infected cells regardless of the major histocompatibility com- plex haplotype of the cell. Our observations provide a biochemical basis for the vaccine function of gp96.

Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus.

The mechanisms by which stress and anti-depressants exert opposite effects on the course of clinical depression are not known. However, potential candidates might include neurotrophic factors that regulate the development, plasticity, and survival of neurons. To explore this hypothesis, we examined the effects of stress and antidepressants on neurotrophin expression in the locus coeruleus (LC), which modulates many of the behavioral and physiological responses to stress and has been implicated in mood disorders. Using in situ hybridization, we demonstrate that neurotrophin 3 (NT-3) is expressed in noradrenergic neurons of the LC. Recurrent, but not acute, immobilization stress increased NT-3 mRNA levels in the LC. In contrast, chronic treatment with antidepressants decreased NT-3 mRNA levels. The effect occurred in response to antidepressants that blocked norepinephrine uptake, whereas serotonin-specific reuptake inhibitors did not alter NT-3 levels. Electroconvulsive seizures also decreased NT-3 expression in the LC as well as the hippocampus. Ntrk3 (neurotrophic tyrosine kinase receptor type 3; formerly TrkC), the receptor for NT-3, is expressed in the LC, but its mRNA levels did not change with stress or antidepressant treatments. Because, NT-3 is known to be trophic for LC neurons, our results raise the possibility that some of the effects of stress and antidepressants on LC function and plasticity could be mediated through NT-3. Moreover, the coexpression of NT-3 and its receptor in the LC suggests the potential for autocrine mechanisms of action.

Energy Signaling in the Regulation of Gene Expression during Stress

Maintenance of homeostasis is pivotal to all forms of life. In the case of plants, homeostasis is constantly threatened by the inability to escape environmental fluctuations, and therefore sensitive mechanisms must have evolved to allow rapid perception of environmental cues and concomitant modification of growth and developmental patterns for adaptation and survival. Re-establishment of homeostasis in response to environmental perturbations requires reprogramming of metabolism and gene expression to shunt energy sources from growth-related biosynthetic processes to defense, acclimation, and, ultimately, adaptation. Failure to mount an initial 'emergency' response may result in nutrient deprivation and irreversible senescence and cell death. Early signaling events largely determine the capacity of plants to orchestrate a successful adaptive response. Early events, on the other hand, are likely to be shared by different conditions through the generation of similar signals and before more specific responses are elaborated. Recent studies lend credence to this hypothesis, underpinning the importance of a shared energy signal in the transcriptional response to various types of stress. Energy deficiency is associated with most environmental perturbations due to their direct or indirect deleterious impact on photosynthesis and/or respiration. Several systems are known to have evolved for monitoring the available resources and triggering metabolic, growth, and developmental decisions accordingly. In doing so, energy-sensing systems regulate gene expression at multiple levels to allow flexibility in the diversity and the kinetics of the stress response.

Putting teeth into the developmental origins hypothesis: A longitudinal study of early childhood malnutrition, enamel hypoplasia and adolescent health in Amazonian Bolivia

Thesis (Ph.D.)--University of Washington, 2016-06

Analysis of the thermal stress behaviour of functionally graded hollow circular cylinders

This paper presents an analysis of the thermomechanical behavior of hollow circular cylinders of functionally graded material (FGM). The solutions are obtained by a novel limiting process that employs the solutions of homogeneous hollow circular cylinders, with no recourse to the basic theory or the equations of non-homogeneous thermoclasticity. Several numerical cases are studied, and conclusions are drawn regarding the general properties of thermal stresses in the FGM cylinder. We conclude that thermal stresses necessarily occur in the FGM cylinder, except in the trivial case of zero temperature. While heat resistance may be improved by sagaciously designing the material composition, careful attention must be paid to the fact that thermal stresses in the FGM cylinder are governed by more factors than are its homogeneous counterparts. The results that are presented here will serve as benchmarks for future related work. (C) 2003 Elsevier Science Ltd. All rights reserved.

The genetic covariance among clinal environments after adaptation to an environmental gradient in Drosophila serrata

We examined the genetic basis of clinal adaptation by determining the evolutionary response of life-history traits to laboratory natural selection along a gradient of thermal stress in Drosophila serrata. A gradient of heat stress was created by exposing larvae to a heat stress of 36degrees for 4 hr for 0, 1, 2, 3, 4, or 5 days of larval development, with the remainder of development taking place at 25degrees. Replicated lines were exposed to each level of this stress every second generation for 30 generations. At the end of selection, we conducted a complete reciprocal transfer experiment where all populations were raised in all environments, to estimate the realized additive genetic covariance matrix among clinal environments in three life-history traits. Visualization of the genetic covariance functions of the life-history traits revealed that the genetic correlation between environments generally declined as environments became more different and even became negative between the most different environments in some cases. One exception to this general pattern was a life-history trait representing the classic trade-off between development time and body size, which responded to selection in a similar genetic fashion across all environments. Adaptation to clinal environments may involve a number of distinct genetic effects along the length of the cline, the complexity of which may not be fully revealed by focusing primarily on populations at the ends of the cline.

Adaptation to being at-risk for Huntington's disease and the availability of genetic testing: Application of a stress and coping model

This study examined the utility of a stress/coping model in explaining adaptation in two groups of people at-risk for Huntington's Disease (HD): those who have not approached genetic testing services (non-testees) and those who have engaged a testing service (testees). The aims were (1) to compare testees and non-testees on stress/coping variables, (2) to examine relations between adjustment and the stress/coping predictors in the two groups, and (3) to examine relations between the stress/coping variables and testees' satisfaction with their first counselling session. Participants were 44 testees and 40 non-testees who completed questionnaires which measured the stress/coping variables: adjustment (global distress, depression, health anxiety, social and dyadic adjustment), genetic testing concerns, testing context (HD contact, experience, knowledge), appraisal (control, threat, self-efficacy), coping strategies (avoidance, self-blame, wishful thinking, seeking support, problem solving), social support and locus of control. Testees also completed a genetic counselling session satisfaction scale. As expected, non-testees reported lower self-efficacy and control appraisals, higher threat and passive avoidant coping than testees. Overall, results supported the hypothesis that within each group poorer adjustment would be related to higher genetic testing concerns, contact with HD, threat appraisals, passive avoidant coping and external locus of control, and lower levels of positive experiences with HD, social support, internal locus of control, self-efficacy, control appraisals, problem solving, emotional approach and seeking social support coping. Session satisfaction scores were positively correlated with dyadic adjustment, problem solving and positive experience with HD, and inversely related to testing concerns, and threat and control appraisals. Findings support the utility of the stress/coping model in explaining adaptation in people who have decided not to seek genetic testing for HD and those who have decided to engage a genetic testing service.

Leukocyte subset responses during exercise under heat stress with carbohydrate or water intake

Purpose: This study investigated leukocyte subset responses to moderate-intensity exercise under heat stress, with water (W) or carbohydrate (CHO) drink ingestion. Methods: In repeated trials, 13 soldiers consumed either a W or CHO drink during 3 h of walking at 4.4 km center dot h(-1) with a 5% gradient (15 min rest per hour) under heat stress (35 C and 55% relative humidity). The soldiers wore combat uniforms and carried water bottles and dummy rifles and ammunition, altogether weighing about 11.5 +/- 1.0 kg. Results: Plasma glucose concentration was significantly higher with CHO than W ingestion during exercise (p < 0.01). There were no significant differences between W and CHO conditions in exercise performance, plasma cortisol concentration, heart rate, or core temperature. CHO ingestion significantly moderated the increases in leukocyte (83% in W, 28% in CHO; p < 0.001), monocyte (60% in W, 34% in CHO; p < 0.05), and granulocyte counts (120% in W, 30% in CHO; p < 0.001), but not in lymphocyte count (41% in W, 25% in CHO). Conclusions: The increases in leukocyte and subset counts during moderate-intensity exercise under heat stress may be comparable to those observed during intense exercise in cool conditions. The response of immune cell counts is blunted by CHO intake during moderate-intensity exercise in the heat, and may not occur through the cortisol pathway.

Response of holosymbiont pigments from the scleractinian coral Montipora monasteriata to short-term heat stress

Heating the scleractinian coral, Montipora monasteriata (Forskal 1775) to 32 degrees C under < 650 mu mol quanta m(-2) s(-1) led to bleaching in the form of a reduction in Peridinin, xanthophyll pool, chlorophyll c(2) and chlorophyll a, but areal dinoflagellates densities did not decline. Associated with this bleaching, chlorophyll (Chl) allomerization and dinoflagellate xanthophyll cycling increased. Chl allomerization is believed to result from the interaction of Chl with singlet oxygen (O-1(2)) or other reactive oxygen species. Thermally induced increases in Chl allomerization are consistent with other studies that have demonstrated that thermal stress generates reactive oxygen species in symbiotic dinoflagellates. Xanthophyll cycling requires the establishment of a pH gradient across the thylakoid membrane. Our results indicate that, during the early stages of thermal stress, thylakoid membranes are intact. Different morphs of M. monasteriata responded differently to the heat stress applied: heavily pigmented coral hosts taken from a high-light environment showed significant reductions in green fluorescent protein (GFP)-like homologues, whereas nonhost pigmented high-light morphs experienced a significant reduction in water-soluble protein content. Paradoxically, the more shade acclimated cave morph were, based on Chl fluorescence data, less thermally stressed than either of the high-light morphs. These results Support the importance of coral pigments for the regulation of the light environment within the host tissue.

Comparative study of symmetric and asymmetric cylindrical MRI gradient Y-coils in terms of induced eddy currents

We have recently introduced the concept of whole-body asymmetric MRI systems [1]. In this theoretical study, we investigate the PNS characteristics of whole-body asymmetric gradient systems as compared to conventional symmetric systems. Recent experimental evidence [2] supports the hypothesis of transverse gradients being the largest contributor of PNS due to induced electric currents. Asymmetric head gradient coils have demonstrated benefits in the past [3]. The numerical results are based on an anatomically-accurate 2mm-human voxel-phantom NORMAN [4]. The results of this study can facilitate the optimization of whole-body asymmetric gradients in terms of patient comfort/safety (less PNS), while prospering the use of asymmetric MRI systems for in-vivo medical interventions.

Reduplication and word stress in Vietnamese

In this paper acoustic properties of two types of reduplicative compound (full and tone sandhi reduplications) were examined to show acoustic evidence of assymetrical prominence relations (van der Hulst, 2005), in support of a hypothesis that Vietnamese reduplications are phonetically right headed and that tone sandhi is a reduction phenomenon occurring on prosodically weak positions (Shih, 2005). The results show phonetic evidence of prosodic constituency at the level of the bisyllabic word in Vietnamese.

MANIFESTAÇÕES PSICOSSOMÁTICAS EM UNIVERSITÁRIOS PORTUGUESES, A PARTIR DA IDENTIFICAÇÃO DE SINTOMAS DE ANSIEDADE, DEPRESSÃO E STRESS

O presente trabalho teve como objetivos investigar a presença de manifestações psicossomáticas em estudantes universitários, a partir da identificação e da prevalência de sintomas de ansiedade, depressão e stress entre outros transtornos; identificar sinais e sintomas de ansiedade, depressão e stress em universitários portugueses; e correlacionar os sinais e sintomas entre si. Utilizou-se o método quantitativo descritivo de corte transversal. Como meio de investigação, foram utilizados três instrumentos: O Inventário de Ansiedade Traço-Estado de Spilberber IDATE, a Escala de Ansiedade, Depressão e Stress EADS-21 (DASS) e o Inventário de Sintomas de Stress para Adultos de Lipp ISSL. A amostra resultou em 147 universitários de primeiro ingresso na universidade com idade variando entre 18 e 26 anos da Universidade do Algarve Ualg (Portugal), em seus diversos cursos. Os dados obtidos foram analisados e correlacionados com o auxilio do software estatístico SPSS - Statistical Package for Social Science (SPSS), versão 19.0 para Windows, utilizando a análise estatística descritiva de frequência e média, Teste T de Student e ANOVA. Os resultados apontaram uma amostra em sua maioria de mulheres, solteiras, que saíram da casa dos pais para estudar e que no momento da coleta dos dados não exerciam atividades de trabalho, apenas estudavam. Houve presença de indicadores de ansiedade, depressão e stress, sendo o nível de ansiedade encontrado moderado e vinculado à probabilidade de depressão associada. Em relação a manifestações psicossomáticas, foi identificada uma dificuldade em auto-avaliação da presença destas, porém entendeu-se que há associação de manifestações psicossomáticas em relação aos sintomas de stress, ansiedade e depressão, encontrados. Levantou-se a hipótese de associação desses sintomas com a situação atual de crise econômica que passa a sociedade portuguesa, principalmente no período de coleta desses dados. Assim, verificou-se um possível estado de vulnerabilidade nesta população com alguma dificuldade em se adaptar às novas exigências de vida, necessitando então de medidas preventivas que auxiliem a adaptação e reestruturação do estilo de vida desses estudantes.

The investigation of the sensitivity gradient of the visual field, as a function of stimulus dynamic range, in the normal and abnormal eye

The study utilized the advanced technology provided by automated perimeters to investigate the hypothesis that patients with retinitis pigmentosa behave atypically over the dynamic range and to concurrently determine the influence of extraneous factors on the format of the normal perimetric sensitivity profile. The perimetric processing of some patients with retinitis pigmentosa was considered to be abnormal in either the temporal and/or the spatial domain. The standard size III stimulus saturated the central regions and was thus ineffective in detecting early depressions in sensitivity in these areas. When stimulus size was scaled in inverse proportion to the square root of ganglion cell receptive field density (M-scaled), isosensitive profiles did not result, although cortical representation was theoretically equivalent across the visual field. It was conjectured that this was due to variations in the ganglion cell characteristics with increasing peripheral angle, most notably spatial summation. It was concluded that the development of perimetric routines incorporating stimulus sizes adjusted in proportion to the coverage factor of retinal ganglion cells would enhance the diagnostic capacity of perimetry. Good general and local correspondence was found between perimetric sensitivity and the available retinal cell counts. Intraocular light scatter arising both from simulations and media opacities depressed perimetric sensitivity. Attenuation was greater centrally for the smaller LED stimuli, whereas the reverse was true for the larger projected stimuli. Prior perimetric experience and pupil size also demonstrated eccentricity-dependent effect on sensitivity. Practice improved perimetric sensitivity for projected stimuli at eccentricities greater than or equal to 30o; particularly in the superior region. Increase in pupil size for LED stimuli enhanced sensitivity at eccentricities greater than 10o. Conversely, microfluctuation in the accommodative response during perimetric examination and the correction of peripheral refractive error had no significant influence on perimetric sensitivity.

A variational conjugate gradient method for determining the fluid velocity of a slow viscous flow

The problem considered is that of determining the fluid velocity for linear hydrostatics Stokes flow of slow viscous fluids from measured velocity and fluid stress force on a part of the boundary of a bounded domain. A variational conjugate gradient iterative procedure is proposed based on solving a series of mixed well-posed boundary value problems for the Stokes operator and its adjoint. In order to stabilize the Cauchy problem, the iterations are ceased according to an optimal order discrepancy principle stopping criterion. Numerical results obtained using the boundary element method confirm that the procedure produces a convergent and stable numerical solution.

The Nrf2-ARE activation protect neurones against oxidative stress

Oxidative stress has been implicated in the pathogenesis of many neurodegenerative diseases including Alzheimer’s disease. The transcription factor, Nrf2 (nuclear factor E2-related factor 2) that binds to the antioxidant responsive element (ARE) activates a battery of genes encoding enzymes and factors essential for neuronal survival. We have investigated the hypothesis that a downstream product of cyclooxygenase(COX-2), 15-deoxy-delta (12, 14)-prostagland in J2 (15d-PGJ2) has protective effects by activating the Nrf2 pathway during oxidative stress.Human neuroblastoma cells (SHSY5Y) were differentiated intoneuronal-like cells as described previously (Gimenez-Cassina et al.,2006). SHSY5Y cells were co-treated with 10 mM buthionine sulfoximine (BSO) 7 10 mM 15d-PGJ2. Cell viability was measured by MTT assay and cellular glutathione (GSH) levels were measured after treating cells for0.5-24 hours by GSH recycling assay. Cellular Nrf2 levels were determined by immunoblotting. IL-6 levels were measured by ELISA.15d-PGJ2 alone lowered GSH levels 30min after the treatment(12.870.64 nmol/mg protein) and returned to untreated control levels at 16hours (28.173.6 nmol/mg protein; Po0.01). Compared to intracellular GSH levels in untreated cells (27.871.8 nmol/mg protein) BSO treatment alone significantly decreased GSH (9.672.1 nmol/mg protein;Po0.001) but co-incubation with 15d-PGJ2 for 24 hours prevented the depletion elicited by BSO(21.372.7 nmol/mg protein). Compared to untreated cells BSO treatment decrease dIL-6 secretion (from 0.941.6ng/ml to 0.6971.3ng/ml) and total Nrf2 protein levels (by21%). Co-incubation with15d-PGJ2 for 24 hours with BSO did not change IL-6(0.6771.4ng/ml) or total Nrf2 level at any time point. This study suggests that neuronal toxicity resulting from glutathione depletion canbere stored by the induction of Nrf2-ARE pathway and the role of the Nrf2 signalling merits further investigation in neurodegenerative diseases.