Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule.

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional profiling revealed that celastrol treatment induces a battery of oxidant defense genes in addition to heat shock genes. Celastrol activated the yeast Yap1 oxidant defense transcription factor via the carboxy-terminal redox center that responds to electrophilic compounds. Antioxidant response genes were likewise induced in mammalian cells, demonstrating that the activation of two major cell stress pathways by celastrol is conserved. We report that celastrol's biological effects, including inhibition of glucocorticoid receptor activity, can be blocked by the addition of excess free thiol, suggesting a chemical mechanism for biological activity based on modification of key reactive thiols by this natural product.

Population structure, inbreeding and local adaptation within an endangered riverine specialist: the nase (Chondrostoma nasus)

Chondrostoma nasus is a cyprinid fish with highly specialized, ecologically and geographically distinct, ontogenetic trophic niches. Nase population numbers across their Swiss range have shown massive declines and many localized extinctions. Here we integrate data from different genetic markers with phenotypic and demographic data to survey patterns of neutral and adaptive genetic diversity in all extant (and one extinct) Swiss nase populations, with the aim to delineate intraspecific conservation units (CUs) and to inform future population management strategies. We discovered two major genetically and geographically distinct population groupings. The first population grouping comprises nase inhabiting rivers flowing into Lake Constance; the second comprises nase populations from Rhine drainages below Lake Constance. Within these clusters there is generally limited genetic differentiation among populations. Genomic outlier scans based on 256–377 polymorphic AFLP loci revealed little evidence of local adaptation both within and among population clusters, with the exception of one candidate locus identified in scans involving the inbred Schanzengraben population. However, significant phenotypic differentiation in body shape between certain populations suggests a need for more intensive future studies of local adaptation. Our data strongly suggests that the two major population groups should be treated as distinct CUs, with any supplemental stocking and reintroductions sourced only from within the range of the CU concerned.

Repeatedly experiencing information overload in a product customization: a case of sequential overchoice

The present study demonstrates how consumers can suffer from sequential overchoice. Customizing a tailor-made suit from combined-attribute choices (e.g., deciding on color and fabric in combination) leads to less satisfaction and less additional consumption than customizing it from single-attribute choices (e.g., deciding on color, then on fabric). The effect is mediated by information overload and moderated by consideration set size.

Balance theory in eWOM: Even if you red-flag this product, I like it, as I dislike you

In eWOM the relationship between the consumer and the reviewer is weak. Still, the present study argues that social information, for example the reviewer`s user picture, influences the product evaluation. By applying balance theory we predict that the evaluation of the recommended product is a function of the induced attitude towards the reviewer and the valence of the review. By utilizing either positive or negative user pictures and either positive or negative reviews, we confirmed the hypothesized interaction. Consumers rated a negatively reviewed product more favorable when the reviewer used a negative user picture, compared to a positive user picture.

Assimilation and contrast in web product reviews: devaluing the recommendation of a proficient but dissimilar reviewer

When viewing web-consumer reviews consumers encounter the reviewers in an anonymous environment. Although their interactions are only virtual they still exchange social information, e.g. often reviewers refer to their proficiency or consumption motives within the review texts. Do these social information harm the viewers’ perception of the recommended products? The present study addresses this question by applying the paradigm of social comparison (Mussweiler, 2003) to web-consumer reviews. In a laboratory experiment with a student sample (n = 120) we manipulated the perceived similarity between reviewer and viewer and the perceived proficiency of the reviewer. A measurement of achievement goals (Elliott & McGregor, 2001) and average number of hours of study prior to the experiment allowed to introduce the reviewer as high [low] in proficiency and similar [dissimilar] in achievement goals. As predicted, the viewer’s evaluation of the recommended products differed as a function of this social information. Contrasting with the reviewer led to devaluing the products recommended by a proficient but dissimilar reviewer. However, against our prediction social comparison with the reviewer did not affect the viewer`s self-evaluation. Whether social information in web-product reviews affects the viewer`s self-evaluation and induces both social comparison processes remains an open question. Future studies aim to address this by manipulating the informational focus of the viewer, rather than the perceived similarity between viewer and reviewer. So far, the present study extends the application of social comparison to consumption environments and contributes to the understanding of the virtual social identity.

The evolution and assessment of pharmaceutical care: Structure, processes, and outcomes

The evolution of pharmaceutical care is identified through a complete review of the literature published in the American Journal of Health-System Pharmacy, the sole comprehensive publication of institutional pharmacy practice. The evolution is categorized according to characteristics of structure (organizational structure, the role of the pharmacist), process (drug delivery systems, formulary management, acquiring drug products, methods to impact drug therapy decisions), and outcomes (cost of drug delivery, cost of drug acquisition and use, improved safety, improved health outcomes) recorded from the 1950s through the 1990s. While significant progress has been made in implementing basic drug distribution systems, levels of pharmacy involvement with direct patient care is still limited.^ A new practice framework suggests enhanced direct patient care involvement through increase in the efficiency and effectiveness of traditional pharmacy services. Recommendations advance internal and external organizational structure relationships that position pharmacists to fully use their unique skills and knowledge to impact drug therapy decisions and outcomes. Specific strategies facilitate expansion of the breadth and scope of each process component in order to expand the depth of integration of pharmacy and pharmaceutical care within the broad healthcare environment. Economic evaluation methods formally evaluate the impact of both operational and clinical interventions.^ Outcome measurements include specific recommendations and methods to increase efficiency of drug acquisition, emphasizing pharmacists' roles that impact physician prescribing decisions. Effectiveness measures include those that improve safety of drug distribution systems, decrease the potential of adverse drug therapy events, and demonstrate that pharmaceutical care can significantly contribute to improvement in overall health status.^ The implementation of the new framework is modeled on a case study at the M.D. Anderson Cancer Center. The implementation of several new drug distribution methods facilitated the redeployment of personnel from distributive functions to direct patient care activities with significant personnel and drug cost reduction. A cost-benefit analysis illustrates that framework process enhancements produced a benefit-to-cost ratio of 7.9. In addition, measures of effectiveness demonstrated significant levels of safety and enhanced drug therapy outcomes. ^

Male Dominance in the New Zealand Longfin Eel Population of a New Zealand River: Probable Causes and Implications for Management

The endemic New Zealand longfin eel Anguilla dieffenbachi (hereafter, longfin eel), is overfished, and in southern South Island, New Zealand, rivers have recently become predominated by males. This study examined length and age at sexual differentiation in male eels in the Aparima River catchment (area, 1,375 km(2); mean flow, 20 m(3.)s(-1)) and the sex ratio and distribution of eels throughout the catchment. Longfin eels differentiated into males mostly at lengths from 300 to 460 mm and ages from 10 to 25+ years. Females were rare: Of 738 eels examined for sexual differentiation, 466 were males and 5 were females, and a few others, not examined, were large enough to be female. These counts suggest a male : female ratio among differentiated longfin eels of 68:1. Of 31 differentiated shortfin eels A. australis, less common in the Aparima River, 26 were females. Male longfin eels were distributed throughout the main stern and tributaries; undifferentiated eels were more prevalent in lower and middle reaches and in the main stem than in upper reaches and tributaries. In other studies, male longfin eels predominated commercial catches in the Aparima and four other southernmost rivers, by 2.4:1 to 13.6:1 males to females. The Aparima River had the most skewed sex ratio. Longfin eel catches from the Aparima River will become more male predominated because few sublegal-size females were present. The length-frequency distributions of eels in the present samples and in the commercial catches were truncated just above minimum legal size (about 460 mm), showing that few females escape the fishery. Historically, females predominated these rivers. The recent change in sex ratio is attributable partly to selective harvest of females, and partly to changes in the structure of the population from fishing, such that differentiation into males has been favored. Longevity, delayed sexual maturity, semel-parity, and endemism with restricted range make the longfin eel particularly vulnerable to overfishing.

Differential Responses of Herbivores and Herbivory to Management in Temperate European Beech

Forest management not only affects biodiversity but also might alter ecosystem processes mediated by the organisms, i.e. herbivory the removal of plant biomass by plant-eating insects and other arthropod groups. Aiming at revealing general relationships between forest management and herbivory we investigated aboveground arthropod herbivory in 105 plots dominated by European beech in three different regions in Germany in the sun-exposed canopy of mature beech trees and on beech saplings in the understorey. We separately assessed damage by different guilds of herbivores, i.e. chewing, sucking and scraping herbivores, gall-forming insects and mites, and leaf-mining insects. We asked whether herbivory differs among different forest management regimes (unmanaged, uneven-aged managed, even-aged managed) and among age-classes within even-aged forests. We further tested for consistency of relationships between regions, strata and herbivore guilds. On average, almost 80 of beech leaves showed herbivory damage, and about 6 of leaf area was consumed. Chewing damage was most common, whereas leaf sucking and scraping damage were very rare. Damage was generally greater in the canopy than in the understorey, in particular for chewing and scraping damage, and the occurrence of mines. There was little difference in herbivory among differently managed forests and the effects of management on damage differed among regions, strata and damage types. Covariates such as wood volume, tree density and plant diversity weakly influenced herbivory, and effects differed between herbivory types. We conclude that despite of the relatively low number of species attacking beech; arthropod herbivory on beech is generally high. We further conclude that responses of herbivory to forest management are multifaceted and environmental factors such as forest structure variables affecting in particular microclimatic conditions are more likely to explain the variability in herbivory among beech forest plots.

Forest structure and composition of previously selectively logged and non-logged montane forests at Mt. Kilimanjaro

The montane forests of Mount Kilimanjaro in Tanzania have been subjected to a long history of selective logging. However, since 1984 logging of indigenous trees is prohibited. Today, these forests allow us to evaluate the long-term effects of selective logging. We mapped the height and diameter at breast height (DBH) of all trees >10 cm DBH on 10 sites of 0.25 ha. Five sites represent non-logged forests, another five selectively logged forests. We tested whether forests were still visibly affected 30–40 years after selective logging in terms of their forest structure and tree diversity. Additionally we compared tree densities of different species guilds, including disturbance-indicator species, late-successional species and main timber species. Furthermore, we specifically compared the community size distributions of selectively logged and non-logged forests, first across all species and then for the most important timber species, Ocotea usambarensis, alone. 30–40 years after selective logging forests still showed a higher overall stem density, mainly due to higher relative abundances of small trees (<50 cm DBH) in general, and higher densities of small size class stems of late-successional species specifically. For O. usambarensis, the selectively logged sites harboured higher relative abundances of small trees and lower relative abundances of harvestable trees. The higher relative abundance of small O. usambarensis-stems in selectively logged forests appears promising for future forest recovery. Thus, outside protected areas, selective logging may be a sustainable management option if logging cycles are considerably longer than 40 years, enough large source trees remain, and the recruiting O. usambarensis individuals find open space for their establishment.

Internet-based stress management for women with preterm labour: a case-based experience report

Pregnant women with preterm labour (PTL) in pregnancy often experience increased distress and anxieties regarding both the pregnancy and the child's health. The pathogenesis of PTL is, among other causes, related to the stress-associated activation of the maternal-foetal stress system. In spite of these psychobiological associations, only a few research studies have investigated the potential of psychological stress-reducing interventions. The following paper will present an online anxiety and stress management self-help program for pregnant women with PTL. Structure and content of the program will be illustrated by a case-based experience report. L.B., 32 years (G3, P1), was recruited at gestational week 27 while hospitalized for PTL for 3 weeks. She worked independently through the program for 6 weeks and had regular written contact with a therapist. Processing the program had a positive impact on L.B.'s anxiety and stress levels, as well as on her experienced depressive symptoms and bonding to the foetus. As PTL and the risk of PTB are associated with distress, psychological stress-reducing interventions might be beneficial. This study examines the applicability of an online intervention for pregnant women with PTL. The case report illustrates how adequate low-threshold psychological support could be provided to these women.

The relationship between top management team innovation orientation and firm growth: The mediating role of firm innovativeness

Upper echelon theory and research on innovation have considered top management teams and their behaviour and characteristics as important factors that positively influence innovativeness and organizational outcomes. Yet, innovation research has mostly focused on individual new product projects, and their performance and impact on firm performance. Recent research has started to apply a more holistic view in terms of innovation, by considering firm-wide innovation instead of single new products. Upper echelon research has concentrated on direct relationships between top management team characteristics and organizational outcomes. But recent research calls for mediating effects of the relationship between top management team characteristics and organizational outcomes. Hence, this study introduces firm innovativeness as a mediator between top management team innovation orientation and firm growth. Focusing on small and medium-sized firms, which often represent highly innovative firms, results show that firm innovativeness fully mediates the relationship between top management team innovation orientation and firm growth. Implications and future research are discussed.