Combined Training Intervention Targeting Medical and Nursing Staff Reduces Ciprofloxacin Use and Events of Urinary Tract Infection.

Inappropriate diagnosis of urinary tract infections (UTI) contributes to antimicrobial overuse. A combined training intervention for medical and nursing staff mainly addressing the analytic process reduced UTI events (9.20 vs. 7.36 per 1000 PD, -20.0%, p = 0.003) and the utilization rate of ciprofloxacin (11.6 vs. 3.5, -69.6 p = 0.001) in a Bavarian University Hospital. Combined training intervention-as part of an antibiotic stewardship program-can be effective in avoiding unnecessary urinalysis and reducing antibiotic consumption.

Satellite telemetry and digital aerial surveys show strong displacement of red-throated divers (Gavia stellata) from offshore wind farms.

Expansion of offshore wind energy is vital for the reduction of CO2 emissions. However, offshore wind farms may negatively impact the environment without proper planning. Here we assess the robustness of the conclusions of earlier studies that the strictly protected red-throated diver, Gavia stellata, is strongly displaced from wind farms in the German Bight (North Sea). We modelled the distribution of divers based on two independent data sets, digital aerial surveys and satellite telemetry, in relation to the dynamic offshore environment and anthropogenic pressures. Both data types found that divers were strongly displaced from wind farms in suitable habitat. The displacement effect gradually decreased with distance from the wind farms (being very strong up to 5 km away), but a significant effect could be detected up to 10-15 km away. The telemetry data further indicated that the displacement distance decreased with decreasing visibility. The displacement distance was also shorter during the day than during the night, potentially as a response to aviation and navigation lights of the wind farms. These findings should be taken into consideration in marine spatial planning to avoid cumulative impacts on red-throated diver populations.

A novel approach for assessing effects of ship traffic on distributions and movements of seabirds.

Marine habitats are nowadays strongly affected by human activities, while for many species the consequences of these impacts are still unclear. The red-throated diver (Gavia stellata) has been reported to be sensitive to ship traffic and other anthropogenic pressures and is consequently of high conservation concern. We studied red-throated divers in the German Bight (North Sea) using satellite telemetry and digital aerial surveys with the aim of assessing effects of ship traffic on the distribution and movements of this species during the non-breeding season. Data from the automatic identification system of ships (AIS) were intersected with bird data and allowed detailed spatial and temporal analyses. During the study period, ship traffic was present throughout the main distribution area of divers. Depending on impact radius, only small areas existed in which ship traffic was present on less than 20% of the days. Ship traffic was dominated by fishing vessels and cargo ships, but also wind farm-related ships were frequently recorded. Red-throated divers were more abundant in areas with no or little concurrent ship traffic. Analysis of aerial survey data revealed strong effects of ship speed on divers: in areas with vessels sailing at high speed only a slow resettlement of the area was observed after the disturbance, while in areas with vessels sailing at medium speed the resettlement was more rapid during the observed time period of 7 hours. Data from satellite-tracking of divers suggest that large relocation distances of individuals are related to disturbance by ships which often trigger birds to take flight. Effective measures to reduce disturbance could include channeled traffic in sensitive areas, as well as speed limits for ships traveling within the protected marine area.

Blocking mTOR Signalling with Rapamycin Ameliorates Imiquimod-induced Psoriasis in Mice.

The mTOR (mechanistic target of rapamycin) inhibitor rapamycin has long been known for its immune suppressive properties, but it has shown limited therapeutic success when given systemically to patients with psoriasis. Recent data have shown that the mTOR pathway is hyperactivated in lesional psoriatic skin, which probably contributes to the disease by interfering with maturation of keratinocytes. This study investigated the effect of topical rapamycin treatment in an imiquimod-induced psoriatic mouse model. The disease was less severe if the mice had received rapamycin treatment. Immunohistological analysis revealed that rapamycin not only prevented the activation of mTOR signalling (P-mTOR and P-S6 levels), but almost normalized the expression of epidermal differentiation markers. In addition, the influx of innate immune cells into the draining lymph nodes was partially reduced by rapamycin treatment. These data emphasize the role of mTOR signalling in the pathogenesis of psoriasis, and support the investigation of topical mTOR inhibition as a novel anti-psoriatic strategy.

Insulin Resistance May Contribute to Upregulation of Adhesion Molecules on Endothelial Cells in Psoriatic Plaques.

Psoriasis primarily affects the skin, but also has a systemic dimension and is associated with severe comorbidities. Since endothelial cells play an important role in psoriasis as well as in the development of cardiovascular comorbidities, we investigated whether a common mechanism, namely cytokine-induced insulin resistance, underlies both pathologies. Activation of the insulin pathway was studied in psoriatic skin and dermal endothelial cells. Expression of adhesion molecules was assessed by flow cytometry, as well as their biological function in flow chamber experiments. The phosphorylation status of Akt, a central kinase in the insulin pathway, suggests that endothelial cells within psoriatic plaques are rendered insulin resistant by pro-inflammatory cytokines. Insulin counteracts the expression of adhesion molecules, but has limited effects on interactions between T cells and endothelial cells. Pro-inflammatory cytokines induce insulin resistance in endothelial cells, which may contribute to the development of the inflammatory infiltrate in psoriasis.

Fitness consequences of northward dispersal as possible adaptation to climate change, using experimental translocation of a migratory passerine.

Climate change leads to rapid, differential changes in phenology across trophic levels, often resulting in temporal mismatches between predators and their prey. If a species cannot easily adjust its timing, it can adapt by choosing a new breeding location with a later phenology of its prey. In this study, we experimentally investigated whether long-distance dispersal to northern breeding grounds with a later phenology could be a feasible process to restore the match between timing of breeding and peak food abundance and thus improve reproductive success. Here, we report the successful translocation of pied flycatchers (Ficedula hypoleuca) to natural breeding sites 560 km to the Northeast. We expected translocated birds to have a fitness advantage with respect to environmental phenology, but to potentially pay costs through the lack of other locally adapted traits. Translocated individuals started egg laying 11 days earlier than northern control birds, which were translocated only within the northern site. The number of fledglings produced was somewhat lower in translocated birds, compared to northern controls, and fledglings were in lower body condition. Translocated individuals were performing not significantly different to control birds that remained at the original southern site. The lack of advantage of the translocated individuals most likely resulted from the exceptionally cold spring in which the experiment was carried out. Our results, however, suggest that pied flycatchers can successfully introduce their early breeding phenotype after dispersing to more northern areas, and thus that adaptation through dispersal is a viable option for populations that get locally maladapted through climate change.

Climate change, breeding date and nestling diet: how temperature differentially affects seasonal changes in pied flycatcher diet depending on habitat variation.

1. Climate warming has led to shifts in the seasonal timing of species. These shifts can differ across trophic levels, and as a result, predator phenology can get out of synchrony with prey phenology. This can have major consequences for predators such as population declines owing to low reproductive success. However, such trophic interactions are likely to differ between habitats, resulting in differential susceptibility of populations to increases in spring temperatures. A mismatch between breeding phenology and food abundance might be mitigated by dietary changes, but few studies have investigated this phenomenon. Here, we present data on nestling diets of nine different populations of pied flycatchers Ficedula hypoleuca, across their breeding range. This species has been shown to adjust its breeding phenology to local climate change, but sometimes insufficiently relative to the phenology of their presumed major prey: Lepidoptera larvae. In spring, such larvae have a pronounced peak in oak habitats, but to a much lesser extent in coniferous and other deciduous habitats. 2. We found strong seasonal declines in the proportions of caterpillars in the diet only for oak habitats, and not for the other forest types. The seasonal decline in oak habitats was most strongly observed in warmer years, indicating that potential mismatches were stronger in warmer years. However, in coniferous and other habitats, no such effect of spring temperature was found. 3. Chicks reached somewhat higher weights in broods provided with higher proportions of caterpillars, supporting the notion that caterpillars are an important food source and that the temporal match with the caterpillar peak may represent an important component of reproductive success. 4. We suggest that pied flycatchers breeding in oak habitats have greater need to adjust timing of breeding to rising spring temperatures, because of the strong seasonality in their food. Such between-habitat differences can have important consequences for population dynamics and should be taken into account in studies on phenotypic plasticity and adaptation to climate change.

PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.

PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.

Translocation as a novel approach to study effects of a new breeding habitat on reproductive output in wild birds.

Environmental conditions under which species reproduce have major consequences on breeding success and subsequent fitness. Therefore breeding habitat choice is ultimately important. Studies rarely address the potential fitness pay-offs of alternative natural breeding habitats by experimental translocation. Here we present a new tool to study fitness consequences of free living birds in different habitats. We translocated a migratory passerine, the pied flycatcher (Ficedula hypoleuca), to a novel site, where pairs were subjected to a short stay (2-4 days) in a nest box-equipped aviary before being released. We show that it is technically possible to retain birds in the new area for breeding, allowing the study of reproductive consequences of dispersal under natural conditions. The translocation resulted in an extension of the interval between arrival and egg laying of four days, highlighting the importance of having an adequate control group. Clutch size and nestling parameters did not differ significantly between translocated and unmanipulated females, which suggests that the procedure did not affect birds in their reproductive performance later on. This method could be applied broadly in evolutionary and ecological research, e.g., to study the potential fitness benefits and costs for dispersing to more northern latitudes as a way of adapting to climate change.

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma.

In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-ß downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

Problem-solving style and multicultural personality dispositions: a study of construct validity.

This exploratory study examined the relationship between problem-solving styles and multicultural personality dispositions among 91 graduate students enrolled in an urban university located in the northeast United States. Problem-solving style was assessed with the three dimensions of the VIEW: an Assessment of Problem Solving Style. Multicultural personality was assessed with the five-factor Multicultural Personality Questionnaire (MPQ); its factors of Cultural Empathy, Open-mindedness, Social Initiative, and Flexibility correlated significantly with Explorer and External problem-solving styles, as predicted. The Emotional Stability subscale also correlated significantly with scores on Explorer style, suggesting that individuals who prefer "thinking in new directions" in problem solving are more likely to report remaining calm under stressful situations. Collectively, study results provided additional evidence of construct validity for the VIEW.

Seasonal changes in colour: a comparison of structural, melanin- and carotenoid-based plumage colours.

BACKGROUND: Plumage coloration is important for bird communication, most notably in sexual signalling. Colour is often considered a good quality indicator, and the expression of exaggerated colours may depend on individual condition during moult. After moult, plumage coloration has been deemed fixed due to the fact that feathers are dead structures. Still, many plumage colours change after moult, although whether this affects signalling has not been sufficiently assessed. METHODOLOGY/PRINCIPAL FINDINGS: We studied changes in coloration after moult in four passerine birds (robin, Erithacus rubecula; blackbird, Turdus merula; blue tit, Cyanistes caeruleus; and great tit, Parus major) displaying various coloration types (melanin-, carotenoid-based and structural). Birds were caught regularly during three years to measure plumage reflectance. We used models of avian colour vision to derive two variables, one describing chromatic and the other achromatic variation over the year that can be compared in magnitude among different colour types. All studied plumage patches but one (yellow breast of the blue tit) showed significant chromatic changes over the year, although these were smaller than for a typical dynamic trait (bill colour). Overall, structural colours showed a reduction in relative reflectance at shorter wavelengths, carotenoid-based colours the opposite pattern, while no general pattern was found for melanin-based colours. Achromatic changes were also common, but there were no consistent patterns of change for the different types of colours. CONCLUSIONS/SIGNIFICANCE: Changes of plumage coloration independent of moult are probably widespread; they should be perceivable by birds and have the potential to affect colour signalling.

The genetic basis of zebra finch vocalizations.

Animal vocalizations play an important role in individual recognition, kin recognition, species recognition, and sexual selection. Despite much work in these fields done on birds virtually nothing is known about the heritability of vocal traits in birds. Here, we study a captive population of more than 800 zebra finches (Taeniopygia guttata) with regard to the quantitative genetics of call and song characteristics. We find very high heritabilities in nonlearned female call traits and considerably lower heritabilities in male call and song traits, which are learned from a tutor and hence show much greater environmental variance than innate vocalizations. In both sexes, we found significant heritabilities in several traits such as mean frequency and measures of timbre, which reflect morphological characteristics of the vocal tract. These traits also showed significant genetic correlations with body size, as well as positive genetic correlations between the sexes, supporting a scenario of honest signaling of body size through genetic pleiotropy ("index signal"). In contrast to such morphology-related voice characteristics, classical song features such as repertoire size or song length showed very low heritabilities. Hence, these traits that are often suspected to be sexually selected would hardly respond to current directional selection.