The long-term stability of self-esteem: Its time-dependent decay and nonzero asymptote

How stable are individual differences in self-esteem? We examined the time-dependent decay of rank-order stability of self-esteem and tested whether stability asymptotically approaches zero or a nonzero value across long test–retest intervals. Analyses were based on 6 assessments across a 29-year period of a sample of 3,180 individuals aged 14 to 102 years. The results indicated that, as test–retest intervals increased, stability exponentially decayed and asymptotically approached a nonzero value (estimated as .43). The exponential decay function explained a large proportion of variance in observed stability coefficients, provided a better fit than alternative functions, and held across gender and for all age groups from adolescence to old age. Moreover, structural equation modeling of the individual-level data suggested that a perfectly stable trait component underlies stability of self-esteem. The findings suggest that the stability of self-esteem is relatively large, even across very long periods, and that self-esteem is a trait-like characteristic.

Differential dynamic properties of scleroderma fibroblasts in response to perturbation of environmental stimuli.

Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-beta pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-beta pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development.

NETWORK TOPOLOGY IN HUMAN PROTEIN INTERACTION DATA PREDICTS FUNCTIONAL ASSOCIATION

High-throughput assays, such as yeast two-hybrid system, have generated a huge amount of protein-protein interaction (PPI) data in the past decade. This tremendously increases the need for developing reliable methods to systematically and automatically suggest protein functions and relationships between them. With the available PPI data, it is now possible to study the functions and relationships in the context of a large-scale network. To data, several network-based schemes have been provided to effectively annotate protein functions on a large scale. However, due to those inherent noises in high-throughput data generation, new methods and algorithms should be developed to increase the reliability of functional annotations. Previous work in a yeast PPI network (Samanta and Liang, 2003) has shown that the local connection topology, particularly for two proteins sharing an unusually large number of neighbors, can predict functional associations between proteins, and hence suggest their functions. One advantage of the work is that their algorithm is not sensitive to noises (false positives) in high-throughput PPI data. In this study, we improved their prediction scheme by developing a new algorithm and new methods which we applied on a human PPI network to make a genome-wide functional inference. We used the new algorithm to measure and reduce the influence of hub proteins on detecting functionally associated proteins. We used the annotations of the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as independent and unbiased benchmarks to evaluate our algorithms and methods within the human PPI network. We showed that, compared with the previous work from Samanta and Liang, our algorithm and methods developed in this study improved the overall quality of functional inferences for human proteins. By applying the algorithms to the human PPI network, we obtained 4,233 significant functional associations among 1,754 proteins. Further comparisons of their KEGG and GO annotations allowed us to assign 466 KEGG pathway annotations to 274 proteins and 123 GO annotations to 114 proteins with estimated false discovery rates of <21% for KEGG and <30% for GO. We clustered 1,729 proteins by their functional associations and made pathway analysis to identify several subclusters that are highly enriched in certain signaling pathways. Particularly, we performed a detailed analysis on a subcluster enriched in the transforming growth factor β signaling pathway (P<10-50) which is important in cell proliferation and tumorigenesis. Analysis of another four subclusters also suggested potential new players in six signaling pathways worthy of further experimental investigations. Our study gives clear insight into the common neighbor-based prediction scheme and provides a reliable method for large-scale functional annotations in this post-genomic era.

Differential dynamic properties of scleroderma fibroblasts in response to perturbation of environmental stimuli.

Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-beta pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-beta pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development.

Cognitive Remediation in early psychosis and in at-risk mental states – Approaches and efficacy

Cognitive Remediation approaches have proven to be effective in enhancing cognitive functions and psychosocial outcomes in multi-episode schizophrenia patients. However, there is a paucity of studies evaluating Cognitive Remediation in first-episode psychosis patients and in those symptomatically at-risk for psychosis. This is despite the growing evidence that impairments in neuro- and social-cognitive functions are already present in early psychosis and even in at-risk mental states and are important predictors of poor outcome, including transition to psychosis. Moreover, Cognitive Remediation applied at younger ages and at earlier stages of schizophrenia yielded greater cognitive and functional gains. Therefore, Cognitive Remediation may be especially appropriate for early intervention. Against this background, we will review and discuss the efficacy of current Cognitive Remediation approaches in early psychosis and in at-risk mental states. Furthermore, we will present novel interventions that are tailored to the specific needs and developmental tasks of patients at-risk for psychosis and aim at improving social and self-referential cognitions as well as interpersonal skills

Study of the cellular mechanism of Sunitinib mediated inactivation of activated hepatic stellate cells and its implications in angiogenesis

The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells (HSC). Inhibition of receptor tyrosine kinase (RTK) signaling showed promise in the treatment of hepatocellular carcinoma. However, there is a lack of knowledge about the effects of RTK inhibitors on the tumor supportive cells. We performed in vitro experiments to study whether Sunitinib, a platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) RTKs' inhibitor, could block both activated HSC functions and angiogenesis and thus prevent the progression of cirrhotic liver to hepatocellular carcinoma. In immortalized human activated HSC LX-2, treatment with Sunitinib 100 nM blocked collagen synthesis by 47%, as assessed by Sirius Red staining, attenuated HSC contraction by 65%, and reduced cell migration by 28% as evaluated using a Boyden's chamber, without affecting cell viability, measured by Trypan blue staining, and apoptosis, measured by propidium iodide (PI) incorporation assay. Our data revealed that Sunitinib treatment blocked the transdifferentiation of primary human HSC (hHSC) to activated myofibroblast-like cells by 65% without affecting hHSC apoptosis and migration. In in vitro angiogenic assays, Sunitinib 100 nM reduced endothelial cells (EC) ring formation by 46% and tube formation by 68%, and decreased vascular sprouting in aorta ring assay and angiogenesis in vascular bed of chick embryo. In conclusion, the present study demonstrates that the RTK inhibitor Sunitinib blocks the activation of HSC and angiogenesis suggesting its potential as a drug candidate in pathological conditions like liver fibrosis and hepatocellular carcinoma.

Brain damage and addictive behavior: a neuropsychological and electroencephalogram investigation with pathologic gamblers.

BACKGROUND Gambling is a form of nonsubstance addiction classified as an impulse control disorder. Pathologic gamblers are considered healthy with respect to their cognitive status. Lesions of the frontolimbic systems, mostly of the right hemisphere, are associated with addictive behavior. Because gamblers are not regarded as "brain-lesioned" and gambling is nontoxic, gambling is a model to test whether addicted "healthy" people are relatively impaired in frontolimbic neuropsychological functions. METHODS Twenty-one nonsubstance dependent gamblers and nineteen healthy subjects underwent a behavioral neurologic interview centered on incidence, origin, and symptoms of possible brain damage, a neuropsychological examination, and an electroencephalogram. RESULTS Seventeen gamblers (81%) had a positive medical history for brain damage (mainly traumatic head injury, pre- or perinatal complications). The gamblers, compared with the controls, were significantly more impaired in concentration, memory, and executive functions, and evidenced a higher prevalence of non-right-handedness (43%) and, non-left-hemisphere language dominance (52%). Electroencephalogram (EEG) revealed dysfunctional activity in 65% of the gamblers, compared with 26% of controls. CONCLUSIONS This study shows that the "healthy" gamblers are indeed brain-damaged. Compared with a matched control population, pathologic gamblers evidenced more brain injuries, more fronto-temporo-limbic neuropsychological dysfunctions and more EEG abnormalities. The authors thus conjecture that addictive gambling may be a consequence of brain damage, especially of the frontolimbic systems, a finding that may well have medicolegal consequences.

Functional proteomics and biochemsitry: working together to unravel mitochondrial phenomena of African trypansomes

Eukaryotic cells are compartmentalized into membrane-bound organelles in order to provide sheltered reaction rooms for various specific processes. Organelles are not randomly distributed in a cell or operate isolated from each other. At the contrary — some organelles are closely linked and their functions are tightly orchestrated. The most well-known example of two such organelles acting in concert are the ER and the mitochondrion that work together in order to coordinate cellular lipid biosynthesis, maintain Ca2+-homeostasis, regulate mitochondrial division and control mitochondrial/ER shape as well as to synchronize the movement of these organelles within a cell. To study the mitochondrion and its interface to the ER requires a simplified mitochondrial system. African trypanosomes represent such a system. The unicellular parasite that causes devastating diseases in humans and animals has only one large mitochondrion that does not undergo fission/fusion events except for the context of cell division. Moreover, mitochondrial functions and morphology are highly regulated throughout the life cycle of the protozoan. Central to the understanding of how mitochondria control their morphology, communicate with their surroundings and manage exchange of metabolites and transport of biopolymers (proteins, RNAs) is the mitochondrial outer membrane (MOM), as the MOM defines the boundary of the organelle. Recently, we have purified the MOM of T. brucei and characterized its proteome using label-free quantitative mass spectrometry for protein abundance profiling in combination with statistical analysis. Our results show that the trypanosomal MOM proteome consists of 82 proteins, two thirds of which have never been associated with mitochondria before. Among these, we identified novel factors required to regulate mitochondrial morphology and the long-elusive protein import machinery of T. brucei. A comparison with the MOM proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. One of these is the Miro-GTPase Gem1. In yeast, this Ca2+-EF-Hand containing polypeptide is thought to be involved in a protein complex that physically tethers the mitochondrion to the ER. Interestingly, a putative tethering complex in mammalian cells was linked to the mitochondrial fusion/fission machinery. Thus, the concept of a protein complex-mediated connection seems to be a general and conserved feature. We are currently investigating, if such a protein complex exists in T. brucei and if the trypanosomal Gem1 protein is involved. This ER-subdomain associated with mitochondria has been termed mitochondria-associated ER-membranes or MAM. The MAM has recently been implicated to play a key role in Alzheimer’s disease. It is therefore of broad and general interest to establish other eukaryotic model systems in order to investigate the MAM-MOM connection in more detail.

Cognitive and physiological effects of an acute physical activity intervention in elementary school children

The aim of the present study was to investigate the effects of an acute physical activity intervention that included cognitive engagement on executive functions and on cortisol level in young elementary school children. Half of the 104 participating children (6–8 years old) attended a 20-min sport sequence, which included cognitively engaging and playful forms of physical activity. The other half was assigned to a resting control condition. Individual differences in children's updating, inhibition, and shifting performance as well as salivary cortisol were assessed before (pre-test), immediately after (post-test), and 40 min after (follow-up) the intervention or control condition, respectively. Results revealed a significantly stronger improvement in inhibition in the experimental group compared to the control group, while it appeared that acute physical activity had no specific effect on updating and shifting. The intervention effect on inhibition leveled out 40 min after physical activity. Salivary cortisol increased significantly more in the experimental compared to the control group between post-test and follow-up and results support partly the assumed inverted U-shaped relationship between cortisol level and cognitive performance. In conclusion, results indicate that acute physical activity that includes cognitive engagement may have immediate positive effects on inhibition, but not necessarily on updating and shifting in elementary school children. This positive effect may partly be explained through cortisol elevation after acute physical activity.

"Sounds Funny? – Humor Effects of Phonological and Prosodic Figures of Speech"

Whereas semantic, logical, and narrative features of verbal humor are well-researched, phonological and prosodic dimensions of verbal funniness are hardly explored. In a 2 × 2 design we varied rhyme and meter in humorous couplets. Rhyme and meter enhanced funniness ratings and supported faster processing. Rhyming couplets also elicited more intense and more positive affective responses, increased subjective comprehensibility and more accurate memory. The humor effect is attributed to special rhyme and meter features distinctive of humoristic poetry in several languages. Verses that employ these formal features make an artful use of typical poetic vices of amateurish poems written for birthday parties or other occasions. Their metrical patterning sounds “mechanical” rather than genuinely “poetic”; they also disregard rules for “good” rhymes. The processing of such verses is discussed in terms of a metacognitive integration of their poetically deviant features into an overall effect of processing ease. The study highlights the importance of nonsemantic rhetorical features in language processing.

Introduction: Sociolinguistics and tourism - mobilities, markets, multilingualism

In the introduction to this special issue on Sociolinguistics and Tourism, we focus on language in tourism as an important window into contemporary forms of economic, political, and social change. Our aim is twofold: (1) to establish and extend ‘sociolinguistics and tourism’ as another social and applied domain of sociolinguistic research; and (2) to use tourism as a lens for a broader discussion of the sociolinguistics of late modernity. To this end, we outline the contours of language and tourism research to date; we consider the (re)conceptualization of key thematics or notions in sociolinguistic research – such as ‘community’, ‘identity’, and ‘language’ itself – as particularly germane to the study of tourism's fleeting encounters; we examine the inevitable tensions between commodification and authenticity; and we explore the links between performances of ‘self’ and ‘other’, and the contestation of different identity positions with regard to social actors’ multilingual repertoires. We illustrate these issues with data examples from several tourist sites, where multilingual resources are deployed for identification, authentication and commodification. Finally, we briefly introduce the papers in this special issue and conclude by commenting on some sociolinguistic consequences of the study of language/s in tourism.

Tracking water pathways in steep hillslopes by d18O depth profiles of soil water

Assessing temporal variations in soil water flow is important, especially at the hillslope scale, to identify mechanisms of runoff and flood generation and pathways for nutrients and pollutants in soils. While surface processes are well considered and parameterized, the assessment of subsurface processes at the hillslope scale is still challenging since measurement of hydrological pathways is connected to high efforts in time, money and personnel work. The latter might not even be possible in alpine environments with harsh winter processes. Soil water stable isotope profiles may offer a time-integrating fingerprint of subsurface water pathways. In this study, we investigated the suitability of soil water stable isotope (d18O) depth profiles to identify water flow paths along two transects of steep subalpine hillslopes in the Swiss Alps. We applied a one-dimensional advection–dispersion model using d18O values of precipitation (ranging from _24.7 to _2.9‰) as input data to simulate the d18O profiles of soil water. The variability of d18O values with depth within each soil profile and a comparison of the simulated and measured d18O profiles were used to infer information about subsurface hydrological pathways. The temporal pattern of d18O in precipitation was found in several profiles, ranging from _14.5 to _4.0‰. This suggests that vertical percolation plays an important role even at slope angles of up to 46_. Lateral subsurface flow and/or mixing of soil water at lower slope angles might occur in deeper soil layers and at sites near a small stream. The difference between several observed and simulated d18O profiles revealed spatially highly variable infiltration patterns during the snowmelt periods: The d18O value of snow (_17.7 ± 1.9‰) was absent in several measured d18O profiles but present in the respective simulated d18O profiles. This indicated overland flow and/or preferential flow through the soil profile during the melt period. The applied methods proved to be a fast and promising tool to obtain time-integrated information on soil water flow paths at the hillslope scale in steep subalpine slopes.

Are shrubs really a sign of declining ecosystem function? Disentangling the myths and truths of woody encroachment in Australia

Since European settlement, there has been a dramatic increase in the density, cover and distribution of woody plants in former grassland and open woodland. There is a widespread belief that shrub encroachment is synonymous with declines in ecosystem functions, and often it is associated with landscape degradation or desertification. Indeed, this decline in ecosystem functioning is considered to be driven largely by the presence of the shrubs themselves. This prevailing paradigm has been the basis for an extensive program of shrub removal, based on the view that it is necessary to reinstate the original open woodland or grassland structure from which shrublands are thought to have been derived. We review existing scientific evidence, particularly focussed on eastern Australia, to question the notion that shrub encroachment leads to declines in ecosystem functions. We then summarise this scientific evidence into two conceptual models aimed at optimising landscape management to maximise the services provided by shrub-encroached areas. The first model seeks to reconcile the apparent conflicts between the patch- and landscape-level effects of shrubs. The second model identifies the ecosystem services derived from different stages of shrub encroachment. We also examined six ecosystem services provided by shrublands (biodiversity, soil C, hydrology, nutrient provision, grass growth and soil fertility) by using published and unpublished data. We demonstrated the following: (1) shrub effects on ecosystems are strongly scale-, species- and environment-dependent and, therefore, no standardised management should be applied to every case; (2) overgrazing dampens the generally positive effect of shrubs, leading to the misleading relationship between encroachment and degradation; (3) woody encroachment per se does not hinder any of the functions or services described above, rather it enhances many of them; (4) no single shrub-encroachment state (including grasslands without shrubs) will maximise all services; rather, the provision of ecosystem goods and services by shrublands requires a mixture of different states; and (5) there has been little rigorous assessment of the long-term effectiveness of removal and no evidence that this improves land condition in most cases. Our review provides the basis for an improved, scientifically based understanding and management of shrublands, so as to balance the competing goals of providing functional habitats, maintaining soil processes and sustaining pastoral livelihoods.

Primary human lung pericytes support and stabilize in-vitro perfusable microvessels.

The formation of blood vessels is a complex tissue-specific process that plays a pivotal role during developmental processes, in wound healing, cancer progression, fibrosis and other pathologies. To study vasculogenesis and vascular remodeling in the context of the lung, we developed an in-vitro microvascular model that closely mimics the human lung microvasculature in terms of 3D architecture, accessibility, functionality and cell types. Human pericytes from the distal airway were isolated and characterized using flow cytometry. To assess their role in the generation of normal microvessels, lung pericytes were mixed in fibrin gel and seeded into well-defined microcompartments together with primary endothelial cells (HUVEC). Patent microvessels covering an area of 3.1 mm2 formed within 3-5 days and were stable for up to 14 days. Soluble signals from the lung pericytes were necessary to establish perfusability, and pericytes migrated towards endothelial microvessels. Cell-cell communication in the form of adherens and tight junctions, as well as secretion of basement membrane was confirmed using transmission electron microscopy and immunocytochemistry on chip. Direct co-culture of pericytes with endothelial cells decreased the microvascular permeability by one order of magnitude from 17.8∙10-6 cm/s to 2.0∙10-6 cm/s and led to vessels with significantly smaller and less variable diameter. Upon phenylephrine administration, vasoconstriction was observed in microvessels lined with pericytes but not in endothelial microvessels only. Perfusable microvessels were also generated with human lung microvascular endothelial cells and lung pericytes. Human lung pericytes were thus shown to have a prominent influence on microvascular morphology, permeability, vasoconstriction and long-term stability in an in-vitro microvascular system. This biomimetic platform opens new possibilities to test functions and interactions of patient-derived cells in a physiologically relevant microvascular setting.

Measurement of long-range pseudorapidity correlations and azimuthal harmonics in √s_NN=5.02 TeV proton-lead collisions with the ATLAS detector

Measurements of two-particle correlation functions and the first five azimuthal harmonics, v 1 to v 5 , are presented, using 28 nb −1 of p+Pb collisions at a nucleon-nucleon center-of-mass energy of √s NN=5.02 TeV measured with the ATLAS detector at the LHC. Significant long-range “ridgelike” correlations are observed for pairs with small relative azimuthal angle (|Δϕ|<π/3 ) and back-to-back pairs (|Δϕ|>2π/3 ) over the transverse momentum range 0.4

and in different intervals of event activity. The event activity is defined by either the number of reconstructed tracks or the total transverse energy on the Pb-fragmentation side. The azimuthal structure of such long-range correlations is Fourier decomposed to obtain the harmonics v n as a function of p T and event activity. The extracted v n values for n=2 to 5 decrease with n . The v 2 and v 3 values are found to be positive in the measured p T range. The v 1 is also measured as a function of p T and is observed to change sign around p T ≈1.5 –2.0 GeV and then increase to about 0.1 for p T >4 GeV. The v 2 (p T ) , v 3 (p T ) , and v 4 (p T ) are compared to the v n coefficients in Pb+Pb collisions at √s NN=2.76 TeV with similar event multiplicities. Reasonable agreement is observed after accounting for the difference in the average p T of particles produced in the two collision systems.