Changes in hippocampal gene expression by 7-nitroindazole in rats submitted to forced swimming stress

Nitric oxide (NO) is an atypical neurotransmitter that has been related to the pathophysiology of major depression disorder. Increased plasma NO levels have been reported in depressed and suicidal patients. Inhibition of neuronial nitric oxide synthase (nNOS), on the other hand, induces antidepressant effects in clinical and pre-clinical trials. The mechanisms responsible for the antidepressant-like effects of nNOS inhibitors, however, are not completely understood. In this study, genomic and proteomic analyses were used to investigate the effects of the preferential nNOS inhibitor 7-nitroindazole (7-NI) on changes in global gene and protein expression in the hippocampus of rats submitted to forced swimming test (FST). Chronic treatment (14 days, i.p.) with imipramine (15 mg/kg daily) or 7-NI (60 mg/kg daily) significantly reduced immobility in the FST. Saturation curves for Serial analysis of gene expression libraries showed that the hippocampus of animals submitted to FST presented a lower number of expressed genes compared to non-FST stressed groups. Imipramine, but not 7-NI, reverted this effect. GeneGo analyses revealed that genes related to oxidative phosphorylation, apoptosis and survival controlled by HTR1A signaling and cytoskeleton remodeling controlled by Rho GTPases were significantly changed by FST. 7-NI prevented this effect. In addition, 7-NI treatment changed the expression of genes related to transcription in the cAMP response element-binding pathway. Therefore, this study suggests that changes in oxidative stress and neuroplastic processes could be involved in the antidepressant-like effects induced by nNOS inhibition.

Response of Saccharomyces cerevisiae to Cadmium and Nickel Stress: The Use of the Sugar Cane Vinasse as a Potential Mitigator

Most of the metals released from industrial activity, among them are cadmium (Cd) and nickel (Ni), inhibit the productivity of cultures and affect microbial metabolism. In this context, the aim of this work was to investigate the capacity of sugar cane vinasse to mitigate the adverse effects of Cd and Ni on cell growth, viability, budding rate and trehalose content of Saccharomyces cerevisiae, likely because of adsorption and chelating action. For this purpose, the yeast was grown batch-wise in YED medium supplemented with selected amounts of vinasse and Cd or Ni. The negative effects of Cd and Ni on S. cerevisiae growth and the mitigating one of sugar cane vinasse were quantified by an exponential model. Without vinasse, the addition of increasing levels of Cd and Ni reduced the specific growth rate, whereas in its presence no reduction was observed. Consistently with the well-proved toxicity of both metals, cell viability and budding rate progressively decreased with increasing their concentration, but in the presence of vinasse the situation was remarkably improved. The trehalose content of S. cerevisiae cells followed the same qualitative behavior as cell viability, even though the negative effect of both metals on this parameter was stronger. These results demonstrate the ability of sugar cane vinasse to mitigate the toxic effects of Cd and Ni.

Increased vascular contractility and oxidative stress in beta(2)-adrenoceptor knockout mice: the role of NADPH oxidase

Background/Aims: beta(2)-adrenoceptor (beta(2)-AR) activation induces smooth muscle relaxation and endothelium-derived nitric oxide (NO) release. However, whether endogenous basal beta(2)-AR activity controls vascular redox status and NO bioavailability is unclear. Thus, we aimed to evaluate vascular reactivity in mice lacking functional beta(2)-AR (beta 2KO), focusing on the role of NO and superoxide anion. Methods and Results: Isolated thoracic aortas from beta 2KO and wild-type mice (WT) were studied. beta 2KO aortas exhibited an enhanced contractile response to phenylephrine compared to WT. Endothelial removal and L-NAME incubation increased phenylephrine-induced contraction, abolishing the differences between beta 2KO and WT mice. Basal NO availability was reduced in aortas from beta 2KO mice. Incubation of beta 2KO aortas with superoxide dismutase or NADPH inhibitor apocynin restored the enhanced contractile response to phenylephrine to WT levels. beta 2KO aortas exhibited oxidative stress detected by enhanced dihydroethidium fluorescence, which was normalized by apocynin. Protein expression of eNOS was reduced, while p47(phox) expression was enhanced in beta 2KO aortas. Conclusions: The present results demonstrate for the first time that enhanced NADPH-derived superoxide anion production is associated with reduced NO bioavailability in aortas of beta 2KO mice. This study extends the knowledge of the relevance of the endogenous activity of beta(2)-AR to the maintenance of the vascular physiology. Copyright (C) 2012 S. Karger AG, Basel

Heat stress impairs performance and induces intestinal inflammation in broiler chickens infected with Salmonella Enteritidis

Stressful situations reduce the welfare, production indices and immune status of chickens. Salmonella spp. are a major zoonotic pathogens that annually cause over 1 billion infections worldwide. We therefore designed the current experiment to analyse the effects of 31 +/- 1 degrees C heat stress (HS) (from 35 to 41 days) on performance parameters, Salmonella invasion and small intestine integrity in broiler chickens infected with Salmonella Enteritidis. We observed that HS decreased body weight gain and feed intake. However, feed conversion was only increased when HS was combined with Salmonella Enteritidis infection. In addition, we observed an increase in serum corticosterone levels in all of the birds that were subjected to HS, showing a hypothalamus-pituitary-adrenal axis activation. Furthermore, mild acute multifocal lymphoplasmacytic enteritis, characterized by foci of heterophil infiltration in the duodenum, jejunum and ileum, was observed in the HS group. In contrast, similar but more evident enteritis was noted in the heat-stressed and Salmonella-infected group. In this group, moderate enteritis was observed in all parts of the small intestine. Lastly, we observed an increase in Salmonella counts in the spleens of the stressed and Salmonella-infected chickens. The combination of HS and Salmonella Enteritidis infection may therefore disrupt the intestinal barrier, which would allow pathogenic bacteria to migrate through the intestinal mucosa to the spleen and generate an inflammatory infiltrate in the gut, decreasing performance parameters.

Vocal and territorial behavior in the Smith frog (Hypsiboas faber): Relationships with plasma levels of corticosterone and testosterone

The possible trade-off between the roles of glucocorticoids as facilitators of energy substrate mobilization and neural inhibitors of sexual behavior during breeding season is under debate. We studied the relationship between calling and territorial behavior with plasma levels of corticosterone (CORT) and plasma levels of testosterone (T) across the breeding season of Hypsiboas faber, a large and territorial Neotropical treefrog. We investigated these relationships through focal observations of males calling naturally, followed by blood sampling for hormonal radioimmunoassay. We additionally used an experimental approach, which consisted of broadcasting recorded advertisement calls for 10 min to simulate an invasion in the territory of the focal subjects, followed by behavioral observation and blood sampling for hormonal radioimmunoassay. Results showed a pattern of co-variation between CORT and T across the breeding season. Furthermore, individual variation in CORT and T was related to different aspects of behavior: individuals with higher CORT showed higher calling rates, and individuals with higher steroid levels, mainly T, showed higher responsivity to social stimulation by other males in the chorus. Experimental simulation of territorial intrusion by using playback of advertisement calls of this species did not elicit consistent changes in agonistic behavior and CORT, but decreased T in focal males. (C) 2012 Elsevier Inc. All rights reserved.

Impact of maternal mild hyperglycemia on maternal care and offspring development and behavior of Wistar rats

The aim of the present study was to evaluate the effect of maternal mild hyperglycemia on maternal behavior, as well as the development, behavior, reproductive function, and glucose tolerance of the offspring. At birth, litters were assigned either to Control (subcutaneous (sc)-citrate buffer) or STZ groups (streptozotocin (STZ)-100 mg/kg-sc.). On PND 90 both STZ-treated and Control female rats were mated. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed during pregnancy. Pregnancy duration, litter size and sex ratio were assessed. Newborns were classified according to birth weight as small (SPA), adequate (APA), or large for pregnancy age (LPA). Maternal behavior was analyzed on PND 5 and 10. Offspring body weight, length, and anogenital distance were measured and general activity was assessed in the open field. Sexual behavior was tested in both male and female offspring. Levels of reproductive hormones and estrous cycle duration were evaluated in female offspring. Female offspring were mated and both a GTT and ITT performed during pregnancy. Neonatal STZ administration caused mild hyperglycemia during pregnancy and changed some aspects of maternal care. The hyperglycemic intrauterine milieu impaired physical development and increased immobility in the open field in the offspring although the latter effect appeared at different ages for males (adulthood) and females (infancy). There was no impairment in the sexual behavior of either male or female offspring. As adults, female offspring of STZ-treated mothers did not show glucose intolerance during pregnancy. Thus, offspring of female rats that show mild hyperglycemia in pregnancy have fewer behavioral and developmental impairments than previously reported in the offspring of severely diabetic dams suggesting that the degree of impairment is directly related to the mother glycemic intensity. (C) 2012 Elsevier Inc. All rights reserved.

Fluoropolymer piezoelectrets with tubular channels: resonance behavior controlled by channel geometry

Ferro- or piezoelectrets are dielectric materials with two elastically very different macroscopic phases and electrically charged interfaces between them. One of the newer piezoelectret variants is a system of two fluoroethylenepropylene (FEP) films that are first laminated around a polytetrafluoroethylene (PTFE) template. Then, by removing the PTFE template, a two-layer FEP structure with open tubular channels is obtained. After electrical charging, the channels form easily deformable macroscopic electric dipoles whose changes under mechanical or electrical stress lead to significant direct or inverse piezoelectricity, respectively. Here, different PTFE templates are employed to generate channel geometries that vary in height or width. It is shown that the control of the channel geometry allows a direct adjustment of the resonance frequencies in the tubular-channel piezoelectrets. By combining several different channel widths in a single ferroelectret, it is possible to obtain multiple resonance peaks that may lead to a rather flat frequency-response region of the transducer material. A phenomenological relation between the resonance frequency and the geometrical parameters of a tubular channel is also presented. This relation may help to design piezoelectrets with a specific frequency response.

Behavioral problems and emotional stress in children with bruxism

Bruxism has a multifactorial etiology, and psychosocial factors have been considered to increase the risk of occurrence of this parafunction. The aim of this study was to evaluate the behavior profile of a group of children diagnosed with bruxism. Eighty 7-11-year-old children of both genders (mean age 8.8 years) first recruited as eligible participants. Twenty-nine children (18 males and 11 females) whose parents/guardians reported to present frequent episodes of tooth grinding/clenching while awake or during sleep (at least 3 nights a week) in the previous 3 months were enrolled in the study. The diagnosis of bruxism was established based on the parents/guardians' report about the children's behavior, habits and possible discomforts in the components of the stomatognathic system allied to the presence of signs and symptoms such as pain on the masticatory muscles, masseter muscle hypertrophy, wear facets, fractures of restorations, dental impressions on the cheek mucosa and tongue. As part of the psychological evaluation, the Rutter's Child Behavior Scale-A2 was applied to the parents/caregivers (one for each child) and the Child Stress Scale was applied to the children. Data were analyzed descriptively based on the frequency of each studied variable. Twenty-four (82.76%) children needed psychological or psychiatric intervention; 17 of them presented neurotic disorders and 7 children presented antisocial disorders. Six (20.70%) children presented significant physical and psychological manifestations of stress. The findings of the present study suggest that behavioral problems and potential emotional problems can be risk factors to bruxism in children.

Theoretical models to predict the mechanical behavior of thick composite tubes

This paper shows theoretical models (analytical formulations) to predict the mechanical behavior of thick composite tubes and how some parameters can influence this behavior. Thus, firstly, it was developed the analytical formulations for a pressurized tube made of composite material with a single thick ply and only one lamination angle. For this case, the stress distribution and the displacement fields are investigated as function of different lamination angles and reinforcement volume fractions. The results obtained by the theoretical model are physic consistent and coherent with the literature information. After that, the previous formulations are extended in order to predict the mechanical behavior of a thick laminated tube. Both analytical formulations are implemented as a computational tool via Matlab code. The results obtained by the computational tool are compared to the finite element analyses, and the stress distribution is considered coherent. Moreover, the engineering computational tool is used to perform failure analysis, using different types of failure criteria, which identifies the damaged ply and the mode of failure.

Towards the stabilization of the low density elements in topology optimization with large deformation

This work addresses the treatment of lower density regions of structures undergoing large deformations during the design process by the topology optimization method (TOM) based on the finite element method. During the design process the nonlinear elastic behavior of the structure is based on exact kinematics. The material model applied in the TOM is based on the solid isotropic microstructure with penalization approach. No void elements are deleted and all internal forces of the nodes surrounding the void elements are considered during the nonlinear equilibrium solution. The distribution of design variables is solved through the method of moving asymptotes, in which the sensitivity of the objective function is obtained directly. In addition, a continuation function and a nonlinear projection function are invoked to obtain a checkerboard free and mesh independent design. 2D examples with both plane strain and plane stress conditions hypothesis are presented and compared. The problem of instability is overcome by adopting a polyconvex constitutive model in conjunction with a suggested relaxation function to stabilize the excessive distorted elements. The exact tangent stiffness matrix is used. The optimal topology results are compared to the results obtained by using the classical Saint Venant–Kirchhoff constitutive law, and strong differences are found.

Maternal immune activation increases the corticosterone response to acute stress without affecting the hypothalamic monoamine content and sleep patterns in male mice offspring

Background/Aims: Early life experiences are homeostatic determinants for adult organisms. We evaluated the impact of prenatal immune activation during late gestation on the neuroimmune-endocrine function of adult offspring and its interaction with acute stress. Methods: Pregnant Swiss mice received saline or lipopolysaccharide (LPS) on gestational day 17. Adult male offspring were assigned to the control or restraint stress condition. We analyzed plasmatic corticosterone and catecholamine levels, the monoamine content in the hypothalamus, striatum and frontal cortex, and the sleep-wake cycle before and after acute restraint stress. Results and Conclusion: Offspring from LPS-treated dams had increased baseline norepinephrine levels and potentiated corticosterone secretion after the acute stressor, and no effect was observed on hypothalamic monoamine content or sleep behavior. The offspring of immune-activated dams exhibited impairments in stress-induced serotonergic and dopaminergic alterations in the striatum and frontal cortex. The data demonstrate a distinction between the plasmatic levels of corticosterone in response to acute stress and the hypothalamic monoamine content and sleep patterns. We provide new evidence regarding the influence of immune activation during late gestation on the neuroendocrine homeostasis of offspring.

Salt stress responses in pear and quince: physiological and molecular aspects

The productivity of agricultural crops is seriously limited by salinity. This problem is rapidly increasing, particularly in irrigated lands. Like almost all the fruit tree species, Pyrus communis is generally considered a salt sensitive species, but only little information is available on its behavior under saline conditions. Previous studies, carried out in the Department of Fruit Tree and Woody Plant Science (University of Bologna), focused their attention on pear and quince salt stress responses to understand which rootstock would be the most suitable for pear in order to tolerate a salt stress condition. It has been reported that pear and quince have different ability in the uptake, translocation and accumulation of chloride (Cl-) and sodium (Na+) ions, when plants were irrigated for one season with saline water (5 dS/m). The aim of the present work was to deepen these aspects and investigate salt stress responses in pear and quince. Two different experiments have been performed: a “short-term” trial in a growth chamber and a “long-term” experiment in the open field. In the short-term experiment, three different genotypes usually adopted as pear rootstocks (MC, BA29 and Farold®40) and the pear variety Abbé Fétel own rooted have been compared under salt stress conditions. The trial was performed in a hydroponic culture system, applying a 90 mM NaCl stress to half of the plants, after five weeks of normal growth in Hoagland’s solution. During the three-weeks of salt stress treatment, physiological, mineral and molecular analyses were performed in order to monitor, for each genotype, the development of the salt stress responses in comparison with the corresponding “unstressed” plants. Farold®40 and Abbé Fétel own rooted showed the onset of leaf necrosis, due to salt toxicity, one week before quinces. Moreover, quinces displayed a significant delay in premature senescence of old leaves, while pears emerged for their ability to regenerate new leaves from apparently dead foliage with the salt stress still running. Physiological measurements, such as shoots length, chlorophyll (Chl) content, and photosynthesis, have been carried out and revealed that pears exhibited a significant reduction in water content and a wilting aspect, while for quinces a decrease in Chl content and a growth slowdown were observed. At the end of the trial, all plants were collected and organs separated for dry weight estimation and mineral analyses (Cu, Fe, Mn, Zn Mg, Ca, K, Na and Cl). Mineral contents have been affected by salinity; same macro/micro nutrients were altered in some organs or relocated within the plant. This plant response could have partially contributed to face the salt stress. Leaves and roots have been harvested for molecular analyses at four different times during stress conditions. Molecular analyses consisted of the gene expression study of three main ion transporters, well known in Arabidopsis thaliana as salt-tolerance determinants in the “SOS” pathway: NHX1 (tonoplast Na+/H+ antiporter), SOS1 (plasmalemma Na+/H+ antiporter) and HKT1 (K+ high-affinity and Na+ low-affinity transporter). These studies showed that two quince rootstocks adopted different responsive mechanisms to NaCl stress. BA29 increased its Na+ sequestration activity into leaf vacuoles, while MC enhanced temporarily the same ability, but in roots. Farold®40, instead, exhibited increases in SOS1 and HKT1 expression mainly at leaf level in the attempt to retrieve Na+ from xylem, while Abbé Fétel differently altered the expression of these genes in roots. Finally, each genotype showed a peculiar response to salt stress that was the sum of its ability in Na+ exclusion, osmotic tolerance and tissue tolerance. In the long-term experiment, potted trees of the pear variety Abbé Fétel grafted on different rootstocks (MC, BA29 and Farold®40), or own rooted and also rootstocks only were subjected to a salt stress through saline water irrigation with an electrical conductivity of 5 dS/m for two years. The purposes of this study were to evaluate salinity effects on physiological (shoot length, number of buds, photosynthesis, etc.) and yield parameters of cultivar Abbé Fétel in the different combinations and to determine the salt amount that pear is able to tolerate over the years. With this work, we confirmed the previous hypothesis that pear, despite being classified as a salt-sensitive fruit tree, can be cultivated for two years under saline water irrigation, without showing any salt toxicity symptoms or severe drawbacks on plant development and production. Among different combinations, Abbé Fétel grafted on MC resulted interesting for its peculiar behaviors under salt stress conditions. In the near future, further investigations on physiological and molecular aspects will be necessary to enrich and broaden the knowledge of salt stress responses in pear.

Shear behavior of reinforced concrete slabs under concentrated load: an investigation through Sequentially Linear Analysis

ABSTRACT (italiano) Con crescente attenzione riguardo al problema della sicurezza di ponti e viadotti esistenti nei Paesi Bassi, lo scopo della presente tesi è quello di studiare, mediante la modellazione con Elementi Finiti ed il continuo confronto con risultati sperimentali, la risposta in esercizio di elementi che compongono infrastrutture del genere, ovvero lastre in calcestruzzo armato sollecitate da carichi concentrati. Tali elementi sono caratterizzati da un comportamento ed una crisi per taglio, la cui modellazione è, da un punto di vista computazionale, una sfida piuttosto ardua, a causa del loro comportamento fragile combinato a vari effetti tridimensionali. La tesi è incentrata sull'utilizzo della Sequentially Linear Analysis (SLA), un metodo di soluzione agli Elementi Finiti alternativo rispetto ai classici approcci incrementali e iterativi. Il vantaggio della SLA è quello di evitare i ben noti problemi di convergenza tipici delle analisi non lineari, specificando direttamente l'incremento di danno sull'elemento finito, attraverso la riduzione di rigidezze e resistenze nel particolare elemento finito, invece dell'incremento di carico o di spostamento. Il confronto tra i risultati di due prove di laboratorio su lastre in calcestruzzo armato e quelli della SLA ha dimostrato in entrambi i casi la robustezza del metodo, in termini di accuratezza dei diagrammi carico-spostamento, di distribuzione di tensioni e deformazioni e di rappresentazione del quadro fessurativo e dei meccanismi di crisi per taglio. Diverse variazioni dei più importanti parametri del modello sono state eseguite, evidenziando la forte incidenza sulle soluzioni dell'energia di frattura e del modello scelto per la riduzione del modulo elastico trasversale. Infine è stato effettuato un paragone tra la SLA ed il metodo non lineare di Newton-Raphson, il quale mostra la maggiore affidabilità della SLA nella valutazione di carichi e spostamenti ultimi insieme ad una significativa riduzione dei tempi computazionali. ABSTRACT (english) With increasing attention to the assessment of safety in existing dutch bridges and viaducts, the aim of the present thesis is to study, through the Finite Element modeling method and the continuous comparison with experimental results, the real response of elements that compose these infrastructures, i.e. reinforced concrete slabs subjected to concentrated loads. These elements are characterized by shear behavior and crisis, whose modeling is, from a computational point of view, a hard challenge, due to their brittle behavior combined with various 3D effects. The thesis is focused on the use of Sequentially Linear Analysis (SLA), an alternative solution technique to classical non linear Finite Element analyses that are based on incremental and iterative approaches. The advantage of SLA is to avoid the well-known convergence problems of non linear analyses by directly specifying a damage increment, in terms of a reduction of stiffness and strength in the particular finite element, instead of a load or displacement increment. The comparison between the results of two laboratory tests on reinforced concrete slabs and those obtained by SLA has shown in both the cases the robustness of the method, in terms of accuracy of load-displacements diagrams, of the distribution of stress and strain and of the representation of the cracking pattern and of the shear failure mechanisms. Different variations of the most important parameters have been performed, pointing out the strong incidence on the solutions of the fracture energy and of the chosen shear retention model. At last a confrontation between SLA and the non linear Newton-Raphson method has been executed, showing the better reliability of the SLA in the evaluation of the ultimate loads and displacements, together with a significant reduction of computational times.

Simulation studies of correlation functions and relaxation in polymeric systems

We investigate the statics and dynamics of a glassy,non-entangled, short bead-spring polymer melt with moleculardynamics simulations. Temperature ranges from slightlyabove the mode-coupling critical temperature to the liquidregime where features of a glassy liquid are absent. Ouraim is to work out the polymer specific effects on therelaxation and particle correlation. We find the intra-chain static structure unaffected bytemperature, it depends only on the distance of monomersalong the backbone. In contrast, the distinct inter-chainstructure shows pronounced site-dependence effects at thelength-scales of the chain and the nearest neighbordistance. There, we also find the strongest temperaturedependence which drives the glass transition. Both the siteaveraged coupling of the monomer and center of mass (CM) andthe CM-CM coupling are weak and presumably not responsiblefor a peak in the coherent relaxation time at the chain'slength scale. Chains rather emerge as soft, easilyinterpenetrating objects. Three particle correlations arewell reproduced by the convolution approximation with theexception of model dependent deviations. In the spatially heterogeneous dynamics of our system weidentify highly mobile monomers which tend to follow eachother in one-dimensional paths forming ``strings''. Thesestrings have an exponential length distribution and aregenerally short compared to the chain length. Thus, arelaxation mechanism in which neighboring mobile monomersmove along the backbone of the chain seems unlikely.However, the correlation of bonded neighbors is enhanced. When liquids are confined between two surfaces in relativesliding motion kinetic friction is observed. We study ageneric model setup by molecular dynamics simulations for awide range of sliding speeds, temperatures, loads, andlubricant coverings for simple and molecular fluids. Instabilities in the particle trajectories are identified asthe origin of kinetic friction. They lead to high particlevelocities of fluid atoms which are gradually dissipatedresulting in a friction force. In commensurate systemsfluid atoms follow continuous trajectories for sub-monolayercoverings and consequently, friction vanishes at low slidingspeeds. For incommensurate systems the velocity probabilitydistribution exhibits approximately exponential tails. Weconnect this velocity distribution to the kinetic frictionforce which reaches a constant value at low sliding speeds. This approach agrees well with the friction obtaineddirectly from simulations and explains Amontons' law on themicroscopic level. Molecular bonds in commensurate systemslead to incommensurate behavior, but do not change thequalitative behavior of incommensurate systems. However,crossed chains form stable load bearing asperities whichstrongly increase friction.

Influence of microstructure variability on short crack growth behavior

Fatigue life in metals is predicted utilizing regression analysis of large sets of experimental data, thus representing the material’s macroscopic response. Furthermore, a high variability in the short crack growth (SCG) rate has been observed in polycrystalline materials, in which the evolution and distributionof local plasticity is strongly influenced by the microstructure features. The present work serves to (a) identify the relationship between the crack driving force based on the local microstructure in the proximity of the crack-tip and (b) defines the correlation between scatter observed in the SCG rates to variability in the microstructure. A crystal plasticity model based on the fast Fourier transform formulation of the elasto-viscoplastic problem (CP-EVP-FFT) is used, since the ability to account for the both elastic and plastic regime is critical in fatigue. Fatigue is governed by slip irreversibility, resulting in crack growth, which starts to occur during local elasto-plastic transition. To investigate the effects of microstructure variability on the SCG rate, sets of different microstructure realizations are constructed, in which cracks of different length are introduced to mimic quasi-static SCG in engineering alloys. From these results, the behavior of the characteristic variables of different length scale are analyzed: (i) Von Mises stress fields (ii) resolved shear stress/strain in the pertinent slip systems, and (iii) slip accumulation/irreversibilities. Through fatigue indicator parameters (FIP), scatter within the SCG rates is related to variability in the microstructural features; the results demonstrate that this relationship between microstructure variability and uncertainty in fatigue behavior is critical for accurate fatigue life prediction.