bluuebunny/crossref_metadata_2025 huggingface dataset:
Tensor‐Virial Equation for Deformation of a Particle in Viscous Sintering
Authors: Wakai F. , Shinoda Y. , Akatsu T.
Published: July 2012

A nonspherical glass particle relaxes to its equilibrium shape by viscous flow driven by capillarity at elevated temperatures. The virial method is applied to Stokes equation for studying the viscous sintering of an ellipsoidal particle. The spheroidization, or the retraction of the particle, is a result of anisotropic deformation driven by the deviatoric components of the sintering stress, which arises from the surface energy tensor. The present simulation of spheroidization is in good agreement with the prediction by the three‐dimensional finite element method. Jackson and Tucker's model on deformation of a liquid droplet can be also understood as a response to the sintering stress.
Development and Validation of a Deontic Justice Scale
Authors: BEUGRÉ CONSTANT D.
Published: July 2012

This paper describes the development and validation of a deontic justice scale (DJS). Study 1 (n = 124) was conducted to test the initial 36‐item version of the scale. It resulted in the reduction of the initial scale to 18 items, including 3 dimensions: moral obligation (8 items), moral accountability (6 items), and moral outrage (4 items). Study 2 (n = 101) was conducted to examine the construct validity and confirm the factor structure of the DJS. Findings from both studies showed evidence of the scale's construct validity. They also showed that deontic justice is a multidimensional construct encompassing moral obligation, moral accountability, and moral outrage. The scale's implications for use as an adequate research instrument are discussed.
Responses of three species of mosquito larvae to the presence of predatory dragonfly and damselfly larvae
Authors: Roberts Derek
Published: July 2012

Although predators have been extensively used in the biological control of mosquito larvae, their efficacy will be reduced if the larvae are able to detect and respond to their presence. This ability to detect and respond to the unseen presence of dragonfly or damselfly larvae was investigated for the larvae of three mosquito species (all Diptera: Culicidae) to see whether they either altered their rate of development or their feeding behaviour. The development of Culex quinquefasciatus Say and Culiseta longiareolata Macquart larvae was not affected by exudates from either predator, but Culex sinaiticus Kirkpatrick developed significantly slower when reared in the presence of a caged dragonfly larva and produced adults that were significantly smaller, indicating that they probably reduced feeding activity to make themselves less detectable to the predator. This only occurred when the dragonflies were fed in situ (in the presence of the mosquito larva) and not when removed for feeding, so that although this removed predator kairomones, other cues such as vibrations caused by movement of the predator may also be involved. In addition, the mosquito larvae responded to dragonfly larvae, but not to damselfly larvae. The depth of the water in which the mosquito larvae were reared had no effect on their response to the dragonfly. All three mosquito species significantly increased surface filter‐feeding, when a predator was present in the water (compared with controls where no predator was present), at the expense of bottom scraping. In Cx. sinaiticus (but not the other two species), surface filter‐feeding was greater when a dragonfly was present, compared with a damselfly. In the experimental conditions of one predator per 250 ml water, all three mosquito species were thus able to detect dragonfly and damselfly larvae (and distinguish between the two), but their response varied among species.
Reproductive output of a female crab spider: the impacts of mating failure, natural enemies, and resource availability
Authors: Morse Douglass H.
Published: July 2012

Female reproductive failure incorporates several variables, of which failure to mate is often an overlooked aspect. Adult female crab spiders, Misumena vatia (Clerck) (Araneae: Thomisidae), seldom fail to mate (maximum of 4.3%), even though meeting males infrequently because of low population densities, female‐skewed adult sex ratios, and failure to provide males with cues for locating them. Females mate with the first male they encounter, but in contrast to the ‘trade‐up’ strategy of many species in this situation, they usually appear to mate only once. During their short season most females that produce a clutch of eggs do not capture enough prey to reach maximum possible size and fecundity, resulting in a nearly 30% loss of potential production. Another ca. 20% fails to accumulate enough mass to lay a clutch. Nest predation and parasitism, primarily by an ichneumonid wasp and a phorid fly, destroy ca. 25% of the clutches. Thus, failure to mate exacts a much lower cost on adult female M. vatia than do several other factors. Mortality of juveniles greatly exceeds that of the adults, with losses of ca. 90% in the first winter and 35% of those surviving to their second winter.
Influence of adhesive point dimension and splint type on splint rigidity – Evaluation by the dynamic Periotest method
Authors: Franz Florian , Potapov Sergej , Petschelt Anselm , Berthold Christine
Published: July 2012

Aim

To evaluate the influence of adhesive point dimension and splint type on the rigidity of wire‐composite splints in vitro.

Materials and Methods

A custom‐made artificial model was used. The two central incisors served as injured teeth (degrees of loosening III and II) and the two lateral incisors as non‐injured teeth (physiological mobility). Horizontal and vertical tooth mobilities were investigated before and after splinting with the Periotest® method; the percent change was taken as the relative splint effect. Teeth were splinted with three types of wire‐composite splints: Dentaflex (0.45 mm), Strengtheners (0.8 × 1.8 mm), and Dentaflex completely covered with composite. Four adhesive point dimensions (2, 3, 4, and 5 mm) were evaluated. Normal distribution was tested with the Kolmogorov–Smirnov test. Differences were evaluated with the anova and post hoc tests for pair‐wise comparisons. Significance level was set at 0.05.

Results

The adhesive point dimension did not influence splint rigidity, in general (
P
 = 0.288). Significant effects were found in non‐injured teeth with the Dentaflex (
P
 < 0.001) and in injured teeth with the Strengtheners (
P
 < 0.001). The Strengtheners splint rigidity increased significantly with increasing adhesive point dimensions. The three splints showed significantly different effects at 5‐mm adhesive point dimension (
P
 < 0.001).

Conclusion

Splint rigidity for injured teeth was influenced by adhesive point dimension only when splinting with Strengtheners. We recommend adapting splint rigidity by selecting different wires and reducing the adhesive point dimension to a minimum. Dentaflex can be used for flexible splinting, Strengtheners, and composite covered Dentaflex for rigid splinting.
The widely invasive tree Pinus radiata facilitates regeneration of native woody species in a semi‐arid ecosystem
Authors: Becerra Pablo I. , Montenegro Gloria
Published: July 2012

Question

What is the effect of invading individuals of the widely invasive species Pinus radiata D. Don on regeneration of native woody species in a semi‐arid ecosystem?

Location

A semi‐arid ecosystem in central Chile.

Methods

We sampled natural regeneration of native woody species in 40 plots in each of three canopy types: (1) under young adult invading trees of P. radiata located in formerly open (disturbed) sites; (2) in patches of native trees; and (3) in open (disturbed) sites, in two localities where this exotic tree is invading. Additionally, we carried out a field experiment in one of these localities; in eight of each of these canopy types we sowed seeds of ten widely distributed woody native species and monitored their recruitment. We also assessed different biotic and abiotic variables in these canopy types.

Results

We found that soil water content, depth and cover of leaf litter were higher and photosythetically active radiation was lower under P. radiata trees and native patches than in open sites. In the natural regeneration study, species richness of seedlings was higher in native patches and under P. radiata trees than in open sites, and total abundance of seedlings (including all species) was higher only in native patches than in open sites. In the field experiment, both species richness and total abundance of seedlings were higher in native patches and under P. radiata trees than in open sites. Moreover, in the field experiment species richness recruiting in native patches was higher than under P. radiata trees.

Conclusions

We suggest that native patches as well as P. radiata trees invading open sites facilitate or have the potential to facilitate regeneration of native species, although facilitation produced by native trees was stronger than that produced by P. radiata. Thus, in sites where nurse plants are not available, invasion by this exotic tree may be exploited in restoration processes through sowing or planting native species under the canopy of invading young trees of P. radiata, eliminating P. radiata individuals after native regeneration has established.
Outside the Church There Is No Death
Authors: Candler Peter M.
Published: July 2012

According to classical Christian doctrine, the human body is not a container for the soul but its “form”. In defending a form of this view, I suggest that the resurrected body of Christ represents the truth of human flesh. In the light of the resurrected and glorified body of Christ, who still bears his wounds, death can be understood as the loss of something irreplaceable and therefore mourned as a horrific deprivation of life; that is, because eternal life consists in the vision of God by our whole selves, and not just a separated soul, a proper Christian anthropology that began in some sense with the glorified body of Christ as the “truth of the physical” might suggest a very different biomedical practice than that with which we are familiar, which often proceeds from a methodological materialism underwritten by a dualistic metaphysics.
Natural Final Causality and Providence in Aquinas
Authors: Barnes Corey L.
Published: July 2012

Thomas Aquinas articulated an understanding of nature that sought to maintain together the integrity of created causality and God's providential ordering of the cosmos. Developing and combining Aristotelian and Neoplatonic approaches to nature and to final causality, Thomas formulated a horizontal or linear final causality wrapped within a larger vertical or circular final causality. This formulation balanced two seemingly opposed principles. First, that natures operate through intrinsic principles toward determinate ends. Second, that non-cognitive agents must be directed toward an end extrinsically. Aquinas balanced these two principles by situating the first within the second such that God creates and directs natures toward determinate ends through divinely bestowed principles intrinsic to those natures. In this way, Aquinas's understanding of providence underlies his approach to nature.
Gilson's Christian Philosophy: A Change in “Tone”
Authors: Fafara Richard
Published: July 2012

Although Étienne Gilson did not change his position on Christian philosophy as defined in his 1931 Gifford Lectures, interesting modifications occur in his later formulations. Whereas Gilson's earlier formulations emphasized philosophy searching within the faith for what can become rational, his later formulations during the 1960s placed more emphasis on its Christian aspect, i.e., faith guiding reason. In the 1960s, Gilson emphasized faith and the Church as the guardians of Christian philosophy, expressed a relative indifference to the validity of rational proofs for the existence of God, and empathized with those accepting questionable philosophical approaches to understand the faith. Post-modernism with its rejection of a “pure” or “scientific” methodology in philosophy serves as an appropriate context in which to situate Gilson's later formulation of Christian philosophy.
Literacy, media and multimodality: a critical response
Authors: Bazalgette Cary , Buckingham David
Published: July 2012

In recent years, literacy educators have increasingly recognised the importance of addressing a broader range of texts in the classroom. This article raises some critical concerns about a particular approach to this issue that has been widely promoted in recent years – the concept of ‘multimodality’. Multimodality theory offers a broadly semiotic approach to analysing a range of communicative forms. It has been widely taken up by literacy educators, initially at an academic level, and has begun to find its way into policy documents, teacher education and professional development and classroom practice. This article presents some criticisms, both of the theory itself and of the ways in which it has been taken up within the wider context of curriculum change. It argues that, in its popular usage, multimodality theory is being appropriated in a way that merely reinforces a long‐standing distinction between print and ‘non‐print’ texts. This contributes in particular to a continuing neglect of the specificity of moving image media – media that are central to the learning and everyday life experiences of young children. Drawing on recent classroom‐based research, the article concludes by offering some brief indications of an alternative approach to these issues.
Kinetic modelling of central carbon metabolism in Escherichia coli
Authors: Peskov Kirill , Mogilevskaya Ekaterina , Demin Oleg
Published: July 2012

In the present study, we developed a detailed kinetic model of Escherichia coli central carbon metabolism. The main model assumptions were based on the results of metabolic and regulatory reconstruction of the system and thorough model verification with experimental data. The development and verification of the model included several stages, which allowed us to take into account both in vitro and in vivo experimental data and avoid the ambiguity that frequently occurs in detailed models of biochemical pathways. The choice of the level of detail for the mathematical description of enzymatic reaction rates and the evaluation of parameter values were based on available published data. Validation of the complete model of the metabolic pathway describing specific physiological states was based on fluxomics and metabolomics data. In particular, we developed a model that describes aerobic growth of E. coli in continuous culture with a limiting concentration of glucose. Such modification of the model was used to integrate experimental metabolomics data obtained in steady‐state conditions for wild‐type E. coli and genetically modified strains, e.g. knockout of the pyruvate kinase gene (pykA). Following analysis of the model behaviour, and comparison of the coincidence between predicted and experimental data, it was possible to investigate the functional and regulatory properties of E. coli central carbon metabolism. For example, a novel metabolic regulatory mechanism for 6‐phosphogluconate dehydrogenase inhibition by phosphoenolpyruvate was hypothesized, and the flux ratios between the reactions catalysed by enzyme isoforms were predicted.

Database The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/peskov/index.html
Functional roles of H98 and W99 and β2α2 loop dynamics in the α‐l‐arabinofuranosidase from Thermobacillus xylanilyticus
Authors: Arab‐Jaziri Faten , Bissaro Bastien , Barbe Sophie , Saurel Olivier , Débat Hélène , Dumon Claire , Gervais Virginie , Milon Alain , André Isabelle , Fauré Régis , O’Donohue Michael J.
Published: July 2012

This study is focused on the elucidation of the functional role of the mobile β2α2 loop in the α‐l‐arabinofuranosidase from Thermobacillus xylanilyticus, and particularly on the roles of loop residues H98 and W99. Using site‐directed mutagenesis, coupled to characterization methods including isothermal titration calorimetry (ITC) and saturation transfer difference nuclear magnetic resonance (STD‐NMR) spectroscopy, and molecular dynamics simulations, it has been possible to provide a molecular level view of interactions and the consequences of mutations. Binding of para‐nitrophenyl α‐l‐arabinofuranoside (pNP‐α‐l‐Araf) to the wild‐type arabinofuranosidase was characterized by Kd values (0.32 and 0.16 mm, from ITC and STD‐NMR respectively) that highly resembled that of the arabinoxylo‐oligosaccharide XA3XX (0.21 mm), and determination of the thermodynamic parameters of enzyme : pNP‐α‐l‐Araf binding revealed that this process is driven by favourable entropy, which is linked to the movement of the β2α2 loop. Loop closure relocates the solvent‐exposed W99 into a buried location, allowing its involvement in substrate binding and in the formation of a functional active site. Similarly, the data underline the role of H98 in the ‘dynamic’ formation and definition of a catalytically operational active site, which may be a specific feature of a subset of GH51 arabinofuranosidases. Substitution of H98 and W99 by alanine or phenylalanine revealed that mutations affected KM and/or kcat. Molecular dynamics performed on W99A implied that this mutation causes the loss of a hydrogen bond and leads to an alternative binding mode that is detrimental for catalysis. STD‐NMR experiments revealed altered binding of the aglycon motif in the active site, combined with reduced STD intensities of the α‐l‐arabinofuranosyl moiety for W99 substitutions.
The role of conserved inulosucrase residues in the reaction and product specificity of Lactobacillus reuteri inulosucrase
Authors: Anwar Munir A. , Leemhuis Hans , Pijning Tjaard , Kralj Slavko , Dijkstra Bauke W. , Dijkhuizen Lubbert
Published: July 2012

The probiotic bacterium Lactobacillus reuteri 121 produces two fructosyltransferase enzymes, a levansucrase and an inulosucrase. Although these two fructosyltransferase enzymes share high sequence similarity, they differ significantly in the type and size distribution of fructooligosaccharide products synthesized from sucrose, and in their activity levels. In order to examine the contribution of specific amino acids to such differences, 15 single and four multiple inulosucrase mutants were designed that affected residues that are conserved in inulosucrase enzymes, but not in levansucrase enzymes. The effects of the mutations were interpreted using the 3D structures of Bacillus subtilis levansucrase (SacB) and Lactobacillus johnsonii inulosucrase (InuJ). The wild‐type inulosucrase synthesizes mostly fructooligosaccharides up to a degree of polymerization of 15 and relatively low amounts of inulin polymer. In contrast, wild‐type levansucrase produces mainly levan polymer and fructooligosaccharides with a degree of polymerization < 5. Although most of the inulosucrase mutants in this study behaved similarly to the wild‐type enzyme, the mutation G416E, at the rim of the active site pocket in loop 415‐423, increased the hydrolytic activity twofold, without significantly changing the transglycosylation activity. The septuple mutant GM4 (T413K, K415R, G416E, A425P, S442N, W486L, P516L), which included two residues from the above‐mentioned loop 415‐423, synthesized 1‐kestose only, but at low efficiency. Mutation A538S, located behind the general acid/base, increased the enzyme activity two to threefold. Mutation N543S, located adjacent to the +1/+2 sub‐site residue R544, resulted in synthesis of not such a wide variety of fructooligosaccharides than the wild‐type enzyme. The present study demonstrates that the product specificity of inulosucrase is easily altered by protein engineering, obtaining inulosucrase variants with higher transglycosylation specificity, higher catalytic rates and different fructooligosaccharide size distributions, without changing the β(2‐1) linkage type in the product.
Stabilization of Water Droplets in Oil with PGPR for Use in Oral and Dermal Applications
Authors: Wolf Frederik , Koehler Karsten , Schuchmann Heike P.
Published: July 2012

To stabilize microstructured fluids, like emulsions, strong surfactants are needed. For oral or dermal applications, these surfactants need to comply with strict legal requirements. Polyglycerin‐polyricinoleat (PGPR) is described as one of the most potent oil‐soluble surfactant in stabilizing water‐in‐oil (W/O) emulsions. Ways were determined to process W/O emulsions with PGPR meeting legal restrictions. The impact of process and recipe parameters on the formation of W/O emulsions was investigated.

It was found that it is possible to stabilize W/O emulsions with very small amounts of PGPR (0.3% in the finished product). Emulsions stabilized with PGPR alone allowed for droplet sizes below 10 µm, but with mostly multimodal droplet size distributions. PGPR showed a strongly increased performance when combined with NaCl in the aqueous phase. This combination allowed for a stabilization of defined, mono‐modal droplet sizes well below 1 µm. Thus, PGPR is under certain conditions an interesting surfactant for stabilization of W/O emulsions, meeting the legal restrictions for the use in oral and dermal applications.

PRACTICAL APPLICATIONS

Microstructured fluids, like emulsions, play an important role within food, cosmetic and pharmaceutical products. They allow for e.g., encapsulation of active agents. To stabilize emulsions for oral and dermal applications, the stabilizing surfactants need to meet legal restrictions. For W/O‐type emulsion, the available surfactants (e.g., PGPR) need to be concentrated too high to work or are very sensitive to environmental impacts (e.g., phospholipids). Thus, results of the study have a potential application in the formulation of W/O emulsions for foods, cosmetics or pharmaceuticals to meet legal requirements.
Predicting Pesticide Attenuation in a Fractured Aquifer Using Lumped‐Parameter Models
Authors: Farlin J. , Gallé T. , Bayerle M. , Pittois D. , Braun C. , El Khabbaz H. , Elsner M. , Maloszewski P.
Published: July 2012

Neighboring springs draining fractured‐rock aquifers can display large differences in water quality and flow regime, depending on local variations of the connectivity and the aperture size distribution of the fracture network. Consequently, because homogeneous equivalent parameters cannot be assumed a priori for the entire regional aquifer, the vulnerability to pollution of such springs has to be studied on a case by case basis. In this paper, a simple lumped‐parameter model usually applied to estimate the mean transit time of water (or tracer) is presented. The original exponential piston‐flow model was modified to take land‐use distribution into account and applied to predict the evolution of atrazine concentration in a series of springs draining a fractured sandstone aquifer in Luxembourg, where despite a nationwide ban in 2005, atrazine concentrations still had not begun to decrease in 2009. This persistence could be explained by exponentially distributed residence times in the aquifer, demonstrating that in some real world cases, models based on the groundwater residence time distribution can be a powerful tool for trend reversal assessments as recommended for instance by current European Union guidelines.
Retracted: Conserving and Extending the Useful Life of the Largest Aquifer in North America: The Future of the High Plains/Ogallala Aquifer
Authors: Sophocleous Marios
Published: July 2012

The water‐level decline of the High Plains/Ogallala aquifer is one of the largest water management concerns in the United States. The economy and livelihood of people living in that vast region depend almost exclusively on water extracted from that aquifer. A debate about its future is ongoing, and questions remain as to how best to conserve the groundwater resource. Maintaining the aquifer will require reductions in pumping and irrigated hectarage and adopting additional conservation measures. Eventually, the agricultural system will have to be based dominantly on the renewable water resources of the region. In effect, this means a limited‐irrigation and/or dry‐farming regime. What Kansas is currently doing to further extend the life of the aquifer is presented here together with additional measures that could be taken. A key management approach to help sustain the aquifer in western Kansas is to divide the aquifer into subunits on which to base localized management decisions. Another recently adopted measure is the establishment of local enhanced management areas, which would allow locally agreed upon specific corrective controls in those areas. History has shown that incentive and voluntary plans alone have not been successful in halting water‐level declines. Thus, limits and timelines need to be set and checks must be in place to enforce strict administration of conservation measures. It is advocated that water laws be reformed and modernized so that “water rights” are constrained by the current availability of water and the preservation of the resource base for future generations.
Distributed Parallel Computing in Stochastic Modeling of Groundwater Systems
Authors: Dong Yanhui , Li Guomin , Xu Haizhen
Published: July 2012

Stochastic modeling is a rapidly evolving, popular approach to the study of the uncertainty and heterogeneity of groundwater systems. However, the use of Monte Carlo‐type simulations to solve practical groundwater problems often encounters computational bottlenecks that hinder the acquisition of meaningful results. To improve the computational efficiency, a system that combines stochastic model generation with MODFLOW‐related programs and distributed parallel processing is investigated. The distributed computing framework, called the Java Parallel Processing Framework, is integrated into the system to allow the batch processing of stochastic models in distributed and parallel systems. As an example, the system is applied to the stochastic delineation of well capture zones in the Pinggu Basin in Beijing. Through the use of 50 processing threads on a cluster with 10 multicore nodes, the execution times of 500 realizations are reduced to 3% compared with those of a serial execution. Through this application, the system demonstrates its potential in solving difficult computational problems in practical stochastic modeling.
Reconciling neuronally and nonneuronally derived acetylcholine in the regulation of immune function
Authors: Kawashima Koichiro , Fujii Takeshi , Moriwaki Yasuhiro , Misawa Hidemi , Horiguchi Kazuhide
Published: July 2012

Immune cells, including lymphocytes, express muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively), and agonist stimulation of these AChRs causes functional and biochemical changes in the cells. The origin of the ACh that acts on immune cell AChRs has remained unclear until recently, however. In 1995, we identified choline acetyltransferase mRNA and protein in human T cells, and found that immunological T cell activation potentiated lymphocytic cholinergic transmission by increasing ACh synthesis and AChR expression. We also found that M1/M5 mAChR signaling upregulates IgG1 and proinflammatory cytokine production, whereas α7 nAChR signaling has the opposite effect. These findings suggest that ACh synthesized by T cells acts as an autocrine and/or paracrine factor via AChRs on immune cells to modulate immune function. In addition, a recently discovered endogenous allosteric α7 nAChR ligand, SLURP‐1, also appears to be involved in modulating normal T cell function.
Expression and functions of μ‐opioid receptors and cannabinoid receptors type 1 in T lymphocytes
Authors: Kraus Jürgen
Published: July 2012

Opioids and cannabinoids modulate T lymphocyte functions. Many effects of the drugs are mediated by μ‐opioid receptor and cannabinoid receptor type 1 (CB1), respectively. These two receptors are strikingly similar with respect to their expression in T cells and the mechanisms by which they mediate modulation of T cell activity. Thus, μ‐opioid receptors and CB1 not expressed in resting primary human and Jurkat T cells. However, in response to the cytokine IL‐4, the epigenetic modifiers 5‐aza‐2′‐deoxycytidine and trichostatin A, and activation of T cells, functional μ‐opioid receptors and CB1 are induced. The induced receptors mediate inhibition of T cell signaling and, thereby, IL‐2 production, a hallmark of activated T cells. Although coupled to inhibitory G proteins, μ‐opioid receptors and CB1 produce a remarkable increase in cAMP levels in T cells stimulated with opioids and cannabinoids, which is a key mechanism for the inhibition of T cell signaling.
Thymic atrophy in acute experimental Chagas disease is associated with an imbalance of stress hormones
Authors: Lepletier Ailin , de Frias Carvalho Vinícius , Morrot Alexandre , Savino Wilson
Published: July 2012

Disorders in the hypothalamic–pituitary–adrenal axis are associated with the pathogenesis of Trypanosoma cruzi infection. During the acute phase of this disease, increased levels of circulating glucocorticoids (GCs) correlate with thymic atrophy. Recently, we demonstrated that this phenomenon is paralleled by a decrease of prolactin (PRL) secretion, another stress hormone that seems to counteract many immunosuppressive effects of GCs. Both GCs and PRL are intrathymically produced and exhibit mutual antagonism through the activation of their respective receptors, GR, and PRLR. Considering that GCs induce apoptosis and inhibit double‐positive (DP) thymocyte proliferation and that PRL administration prevents these effects, it seems plausible that a local imbalance of GR–PRLR crosstalk underlies the thymic involution occurring in acute T. cruzi infection. In this respect, preserving PRLR signaling seems to be crucial for protecting DP from GC‐induced apoptosis.
Role of sleep in the regulation of the immune system and the pituitary hormones
Authors: Gómez‐González Beatriz , Domínguez‐Salazar Emilio , Hurtado‐Alvarado Gabriela , Esqueda‐Leon Enrique , Santana‐Miranda Rafael , Rojas‐Zamorano Jose Angel , Velázquez‐Moctezuma Javier
Published: July 2012

Sleep is characterized by a reduced response to external stimuli and a particular form of electroencephalographic (EEG) activity. Sleep is divided into two stages: REM sleep, characterized by muscle atonia, rapid eye movements, and EEG activity similar to wakefulness, and non‐REM sleep, characterized by slow EEG activity. Around 80% of total sleep time is non‐REM. Although it has been intensely studied for decades, the function (or functions) of sleep remains elusive. Sleep is a highly regulated state; some brain regions and several hormones and cytokines participate in sleep regulation. This mini‐review focuses on how pituitary hormones and cytokines regulate or affect sleep and how sleep modifies the plasma concentration of hormones as well as cytokines. Also, we review the effects of hypophysectomy and some autoimmune diseases on sleep pattern. Finally, we propose that one of the functions of sleep is to maintain the integrity of the neuro–immune–endocrine system.
Hsp72, inflammation, and aging: causes, consequences, and perspectives
Authors: Ortega Eduardo , Bote María Elena , Besedovsky Hugo Oscar , Rey Adriana del
Published: July 2012

Although aging is an inexorable component of life, its progress depends on how cumulative disruptions of homeostasis are compensated. Cumulative oxidative and inflammatory processes must be controlled to maintain successful aging. Heat shock proteins, such as those of the Hsp70 family, can be considered a danger signal, and their effects can either support longevity by neutralizing danger or can become detrimental when their production is not balanced. Here, we discuss evidence indicating that these highly conserved proteins can favor longevity when such balance is achieved. We emphasize mechanisms affected by Hsp72 that can interfere with effects of excessive oxidative stress and subtle inflammation and, acting either directly or by affecting neuro‐immune‐endocrine interactions, can mediate metabolic, neuroprotective, and behavioral adjustments during the aging process.
Chronic neuropathic pain–like behavior and brain‐borne IL‐1β
Authors: del Rey Adriana , Apkarian A. Vania , Martina Marco , Besedovsky Hugo O.
Published: July 2012

Neuropathic pain in animals results in increased IL‐1β expression in the damaged nerve, the dorsal root ganglia, and the spinal cord. Here, we discuss our results showing that this cytokine is also overexpressed at supraspinal brain regions, in particular in the contralateral side of the hippocampus and prefrontal cortex and in the brainstem, in rats with neuropathic pain‐like behavior. We show that neuropathic pain degree and development depend on the specific nerve injury model and rat strain studied, and that there is a correlation between hippocampal IL‐1β expression and tactile sensitivity. Furthermore, the correlations between hippocampal IL‐1β and IL‐1ra or IL‐6 observed in control animals, are disrupted in rats with increased pain sensitivity. The lateralization of increased cytokine expression indicates that this alteration may reflect nociception. The potential functional consequences of increased IL‐1β expression in the brain during neuropathic pain are discussed.
Experimental endotoxemia as a model to study neuroimmune mechanisms in human visceral pain
Authors: Benson Sven , Engler Harald , Schedlowski Manfred , Elsenbruch Sigrid
Published: July 2012

The administration of bacterial endotoxin (i.e., lipopolysaccharide, LPS) constitutes a well‐established experimental approach to study the effects of an acute and transient immune activation on physiological, behavioral, and emotional aspects of sickness behavior in animals and healthy humans. However, little is known about possible effects of experimental endotoxemia on pain in humans. This knowledge gap is particularly striking in the context of visceral pain in functional as well as chronic‐inflammatory gastrointestinal disorders. Although inflammatory processes have been implicated in the pathophysiology of visceral pain, it remains incompletely understood how inflammatory mediators interact with bottom–up (i.e., increased afferent input) and top–down (i.e., altered central pain processing) mechanisms of visceral hyperalgesia. Considering the recent findings of visceral hyperalgesia after LPS application in humans, in this review, we propose that experimental endotoxemia with its complex peripheral and central effects constitutes an experimental model to study neuroimmune communication in human pain research. We summarize and attempt to integrate relevant animal and human studies concerning neuroimmune communication in visceral and somatic pain, discuss putative mechanisms, and conclude with future research directions.
Presentation of neuroendocrine self in the thymus: a necessity for integrated evolution of the immune and neuroendocrine systems
Authors: Geenen Vincent
Published: July 2012

During evolution, from ancestor thymoids scattered in gill baskets of the lamprey, the first unique thymus appeared in jawed cartilaginous fishes around 450–500 millions years ago, concomitantly or shortly after the emergence of recombinase‐dependent adaptive immunity. The major biological function of the thymus is to generate a diverse repertoire of T cell receptors that are self tolerant. The thymus achieves this role by using two complementary and intimately associated mechanisms: apoptotic deletion of T cell clones bearing a TCR with high affinity for self‐antigens presented by MHC proteins on thymic epithelial cells (TECs) and dendritic cells (DCs); and generation of self‐antigen–specific natural regulatory T (nTreg) cells. Moreover, the escape from thymic central self‐tolerance plays a primary role in the development of autoimmune diseases that are a significant burden for the quality of life and health‐care cost. Our new knowledge in thymus physiology and physiopathology is currently translated into innovative therapeutic strategies against these devastating chronic diseases.
Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction
Authors: Silverman Marni N. , Sternberg Esther M.
Published: July 2012

Enhanced susceptibility to inflammatory and autoimmune disease can be related to impairments in HPA axis activity and associated hypocortisolism, or to glucocorticoid resistance resulting from impairments in local factors affecting glucocorticoid availability and function, including the glucocorticoid receptor (GR). The enhanced inflammation and hypercortisolism that typically characterize stress‐related illnesses, such as depression, metabolic syndrome, cardiovascular disease, or osteoporosis, may also be related to increased glucocorticoid resistance. This review focuses on impaired GR function as a molecular mechanism of glucocorticoid resistance. Both genetic and environmental factors can contribute to impaired GR function. The evidence that glucocorticoid resistance can be environmentally induced has important implications for management of stress‐related inflammatory illnesses and underscores the importance of prevention and management of chronic stress. The simultaneous assessment of neural, endocrine, and immune biomarkers through various noninvasive methods will also be discussed.
Role of interleukin‐6 in stress, sleep, and fatigue
Authors: Rohleder Nicolas , Aringer Martin , Boentert Matthias
Published: July 2012

Chronic low‐grade inflammation, in particular increased concentrations of proinflammatory cytokines such as interleukin (IL)‐6 in the circulation, is observed with increasing age, but it is also as a consequence of various medical and psychological conditions, as well as life‐style choices. Since molecules such as IL‐6 have pleiotropic effects, consequences are wide ranging. This short review summarizes the evidence showing how IL‐6 elevations in the context of inflammatory disease affect the organism, with a focus on sleep‐related symptoms and fatigue; and conversely, how alterations in sleep duration and quality stimulate increased concentrations of IL‐6 in the circulation. Research showing that acute as well as chronic psychological stress also increase concentrations of IL‐6 supports the notion of a close link between an organism's response to physiological and psychological perturbations. The findings summarized here further underscore the particular importance of IL‐6 as a messenger molecule that connects peripheral regulatory processes with the CNS.
Antidepressants prevent hierarchy destabilization induced by lipopolysaccharide administration in mice: a neurobiological approach to depression
Authors: Cohn Daniel Wagner Hamada , Kinoshita Denise , Palermo‐Neto João
Published: July 2012

In spite of the high prevalence and negative impact of depression, little is known about its pathophysiology. Basic research on depression needs new animal models in order to increase knowledge of the disease and search for new therapies. The work presented here aims to provide a neurobiologically validated model for investigating the relationships among sickness behavior, antidepressants treatment, and social dominance behavior. For this purpose, dominant individuals from dyads of male Swiss mice were treated with the bacterial endotoxin lipopolysaccharide (LPS) to induce social hierarchy destabilization. Two groups were treated with the antidepressants imipramine and fluoxetine prior to LPS administration. In these groups, antidepressant treatment prevented the occurrence of social destabilization. These results indicate that this model could be useful in providing new insights into the understanding of the brain systems involved in depression.
Growth hormone modulates migration of thymocytes and peripheral T cells
Authors: Savino Wilson , Smaniotto Salete , Mendes‐da‐Cruz Daniella Arêas , Dardenne Mireille
Published: July 2012

In the context of immunoneuroendocrine cross talk, growth hormone (GH) exerts pleiotropic effects in the immune system. For example, GH‐transgenic mice, as well as animals and humans treated with GH, exhibit enhanced cellularity in the thymus. GH also stimulates the thymic microenvironment, augmenting chemokine and extracellular matrix (ECM) production, with consequent increase in ECM‐ and chemokine‐driven thymocyte migratory responses. Peripheral T cell migration triggered by laminin or fibronectin was enhanced in cells from GH‐transgenic versus wild‐type control adult mice, as seen for CD4+ and CD8+ T cells from mesenteric lymph nodes. Migration of these T lymphocytes, triggered by the chemokine CXCL12, in conjunction with laminin or fibronectin, was also enhanced compared with control counterparts. Considering that GH can be used as an adjuvant therapy in immunodeficiencies, including AIDS, the concepts defined herein, that GH enhances developing and peripheral T cell migration, provide new clues for future GH‐related immune interventions.
Transforming growth factor‐beta inhibits the expression of clock genes
Authors: Gast Heidemarie , Gordic Sonja , Petrzilka Saskia , Lopez Martin , Müller Andreas , Gietl Anton , Hock Christoph , Birchler Thomas , Fontana Adriano
Published: July 2012

Disturbances of sleep–wake rhythms are an important problem in Alzheimer's disease (AD). Circadian rhythms are regulated by clock genes. Transforming growth factor‐beta (TGF‐β) is overexpressed in neurons in AD and is the only cytokine that is increased in cerebrospinal fluid (CSF). Our data show that TGF‐β2 inhibits the expression of the clock genes Period (Per)1, Per2, and Rev‐erbα, and of the clock‐controlled genes D‐site albumin promoter binding protein (Dbp) and thyrotroph embryonic factor (Tef). However, our results showed that TGF‐β2 did not alter the expression of brain and muscle Arnt‐like protein‐1 (Bmal1). The concentrations of TGF‐β2 in the CSF of 2 of 16 AD patients and of 1 of 7 patients with mild cognitive impairment were in the dose range required to suppress the expression of clock genes. TGF‐β2–induced dysregulation of clock genes may alter neuronal pathways, which may be causally related to abnormal sleep–wake rhythms in AD patients.
T cells affect central and peripheral noradrenergic mechanisms and neurotrophin concentration in the spleen and hypothalamus
Authors: Jouda Jamela , Wildmann Johannes , Schäfer Martin , Roggero Eduardo , Besedovsky Hugo O. , del Rey Adriana
Published: July 2012

Interactions between T cells and noradrenergic pathways were investigated using athymic nude mice as a model. Higher noradrenaline (NA) concentrations and increased density of noradrenergic fibers were found in the spleen and hypothalamus, but not in the kidney, of 21‐day‐old Foxn1n (athymic) mice, compared with Foxn1n/Foxn1+ (heterozygous) littermates. Although no differences in nerve growth factor concentrations were detected, significantly higher brain‐derived neurotrophic factor concentrations were found in the spleen and hypothalamus of athymic mice compared with the controls. All of these alterations were abrogated in Foxn1n mice reconstituted by thymus transplantation at birth. These results suggest that T lymphocytes or their products can induce (1) a decrease in the number and activity in splenic sympathetic nerve fibers; (2) a decrease in NA content in the hypothalamus, which, in turn, may influence the pituitary–adrenal axis and the descending neural pathways associated with the autonomic nervous system; and (3) changes in neurotrophin concentration in the spleen and hypothalamus.
Changes in the immune and endocrine responses of patients with pulmonary tuberculosis undergoing specific treatment
Authors: Bongiovanni Bettina , Díaz Ariana , D’Attilio Luciano , Santucci Natalia , Dídoli Griselda , Lioi Susana , Nannini Luis J. , Gardeñez Walter , Bogue Cristina , Besedovsky Hugo , del Rey Adriana , Bottasso Oscar , Bay María Luisa
Published: July 2012

We evaluated immune and endocrine status following antituberculosis treatment in HIV‐negative patients with newly diagnosed tuberculosis (TB). Treatment led to a decrease in IL‐6, IL‐1β, and C‐reactive protein levels. Cortisol levels decreased throughout the anti‐TB treatment, particularly after 4 months, but changes were less pronounced than those seen in proinflammatory mediators. Specific therapy resulted in increased dehydroepiandrosterone (DHEA) levels, which peaked after 4 months and started to decline after 6 months of treatment, reaching levels below those detected at inclusion. In contrast, in most patients, dehydroepiandrosterone sulfate (DHEAS) levels remained unchanged, although a trend toward increased concentrations was observed in a few cases 3 months after the treatment was finished. Specific therapy also resulted in more balanced cortisol/DHEA and cortisol/DHEAS ratios. Etiologic treatment involves favorable immune and endocrine changes, which may account for its beneficial effects.
Different peripheral neuroendocrine responses to Trypanosoma cruzi infection in mice lacking adaptive immunity
Authors: Roggero Eduardo , Wildmann Johannes , Passerini Marcelo O. , del Rey Adriana , Besedovsky Hugo O.
Published: July 2012

Trypanosoma cruzi infection in mice triggers neuroendocrine responses that affect the course of the disease. To analyze the contribution of adaptive immunity to these responses, comparative studies between normal C57Bl/6J and recombinase activator gene 1 (RAG‐1)–deficient mice, which lack mature B and T lymphocytes, were performed. There was no difference between both types of mice in basal body weight. Following infection, higher parasitemia, increased IL‐1β and IL‐6 blood levels, less marked changes in lymphoid organs weight, no cardiomegaly, and earlier mortality were observed in RAG‐1–deficient, compared with normal mice. The response of the hypothalamus–pituitary–adrenal axis after infection occurred earlier and was more intense in RAG‐1–deficient mice than in normal mice. Noradrenaline concentration and serotonergic metabolism in the spleen, lymph nodes, and heart differed between RAG‐1–deficient and normal mice. Our studies indicate that the absence of adaptive immunity to T. cruzi influences the neuroendocrine response to the infection with this parasite.
Regulation of intestinal morphology and GALT by pituitary hormones in the rat
Authors: Cárdenas‐Jaramillo Luz María , Quintanar‐Stephano Andrés , Jarillo‐Luna Rosa Adriana , Rivera‐Aguilar Víctor , Oliver‐Aguillón Gabriela , Campos‐Rodríguez Rafael , Kovacs Kalman , Berczi Istvan
Published: July 2012

Here, the effects of neurointermediate (NIL), anterior (AL), and total hypophysectomy (HYPOX) on ileal mucosa cells and gut‐associated lymphoid tissue (GALT) are reported. Compared with the sham‐operated (SHAM) rats, the villi height and goblet cells numbers were significantly decreased in all groups. Lamina propria area decreased in AL and HYPOX, but not in NIL animals. CD8+ but not CD4+ lymphocytes decreased in the HYPOX and NIL groups. Paneth cells did not change, while IgA cells, IgM cells, and secretory IgA were significantly decreased in all groups. NIL but not AL animals lost significant numbers of IgA cells and secretory IgA. In summary, pituitary hormones exert lobe‐specific regulatory effects on the gut and on GALT.