Tularemia in a common marmoset (Callithrix jacchus) diagnosed by 16S rRNA sequencing

We report a case of tularemia in a common marmoset (Callithrix jacchus) diagnosed by determination of the isolate's 16S ribosomal RNA (rRNA) gene sequence. Pathological examination of the animal revealed a multifocal acute necrotizing hepatitis, interstitial nephritis, splenitis, and lymphangitis of the mandibular, retropharyngeal, and cervical and mesenteric lymph nodes. Moreover, multiple foci of acute necrosis were found in the epithelium of the jejunum and the interstitium of the lung. Bacteriological investigations revealed a septicemia. The isolated infectious agent was uncommon, not routinely diagnosed in our laboratory and therefore difficult to identify by conventional tools in a reasonable time and effort. thus, we decided to perform a genetic analysis based on the 16S rRNA gene sequence. Thereby, an infection with Francisella tularensis, the causative agent of tularemia, was unambiguously diagnosed. This shows the great advantage 16S rRNA gene sequencing has as a general identification approach for unusual or rare isolates.

Schul-, Praxis- und habituelles Herrschaftswissen. Bildung ländlicher Eliten mit Blick auf die korporative Selbstverwaltung in der frühmodernen Schweiz (18. und 19. Jahrhundert)

Knowledge taught at schools, everyday skills and practical know-how. The relevancy of formation for local elites and the corporative self-government of Early Modern Switzerland Daniel Schläppi, Bern There were different kinds of rural elites in Early Modern Switzerland. The diverse parts of the country developed in very dissimilar ways politically and economically. Some regions were dominated by traditional types of agriculture. Some territories were ruled by major cities. In some of the rural Cantons like Uri, Schwyz, Unterwalden, Glarus and Zug a political elite took control over generations and practiced a cultural lifestyle comparable to the famous aristocracies in cities like Bern, Basel, Freiburg, Luzern, Solothurn and Zurich. Intense proto-industrialization formed a completely different sort of elite with strong affinities to industry and trade in other regions. Meanwhile the habitants of the valley close-by stayed farmers like their ancestors (like in Appenzell). In the most conservative parts of the country mercenary business played an important role till the very end of the Ancien Regime and even furthermore. In summery the variety of historical circumstances caused heterogeneous elites all over. Such socio-political diversity provoked a variety of educational backgrounds. I an academic understanding of the term we know only little about literacy in local rural elites. But there is strong evidence that a lively culture of reading and story-telling existed. This means that even simple countrymen seem to have been in possession of some books. The organisation and capacity of the school system is subject of controversial discussions among up to date researchers. The state of research makes us suppose that the people designed to political careers learned their essential skills not only in school but also in everyday life or on the job. Based on the fact that every community and countless public corporations managed their affairs by their own it’s evident that the local elite’s key-players had a large repertoire of techniques and skills like writing, calculating, strategic thinking or knowledge of oral tradition, old usage or important rituals. Unfortunately the historical actors left not that many sources that would tell us precisely how knowledge and know-how were transferred in former times. Hardly any private account books or common correspondence have been conserved. But a huge bunch of sources that originate from corporative self-administration shows us that most local elites were well-educated and had the necessary skills anyway. Above all other sources like for instance the «Topographische Beschreibungen» (topographic descriptions) that were initiated by the «Ökonomische Gesellschaft» of Berne since the sixties of the 18th century provide an insight into pre-modern classrooms. More important information on the historical formation-reality can be gained by the autobiography of the famous poor peasant Ulrich Bräker (1735‒1798) or some of the novels by Albert Bitzius (1797‒1854, better known as Jeremias Gotthelf). The pedagogic writings by Johann Heinrich Pestalozzi (1746‒1827) and the influences by his mentors Johann Rudolf Tschiffeli (1716‒1780) or Philipp Emanuel von Fellenberg (1771‒1884) are quite illustrative as well.

Health-related quality of life in rural children living in four European countries: the GABRIEL study

OBJECTIVE Measuring children's health-related quality of life (HRQOL) is of growing importance given increasing chronic diseases. By integrating HRQOL questions into the European GABRIEL study, we assessed differences in HRQOL between rural farm and non-farm children from Germany, Austria, Switzerland and Poland to relate it to common childhood health problems and to compare it to a representative, mostly urban German population sample (KIGGS). METHODS The parents of 10,400 school-aged children answered comprehensive questionnaires including health-related questions and the KINDL-R questions assessing HRQOL. RESULTS Austrian children reported highest KINDL-R scores (mean: 80.9; 95 % CI [80.4, 81.4]) and Polish children the lowest (74.5; [73.9, 75.0]). Farm children reported higher KINDL-R scores than non-farm children (p = 0.002). Significantly lower scores were observed in children with allergic diseases (p < 0.001), with sleeping difficulties (p < 0.001) and in overweight children (p = 0.04). The German GABRIEL sample reported higher mean scores (age 7-10 years: 80.1, [79.9, 80.4]; age 11-13 years: 77.1, [74.9, 79.2]) compared to the urban KIGGS study (age 7-10 years: 79.0, [78.7-79.3]; age 11-13 years: 75.1 [74.6-75.6]). Socio-demographic or health-related factors could not explain differences in HRQOL between countries. CONCLUSIONS Future increases in chronic diseases may negatively impact children's HRQOL.

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, β-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.

Sex-specific clines support incipient speciation in a common European mammal

Hybrid zones provide excellent opportunities to study processes and mechanisms underlying reproductive isolation and speciation. Here we investigated sex-specific clines of molecular markers in hybrid zones of morphologically cryptic yet genetically highly-diverged evolutionary lineages of the European common vole (Microtus arvalis). We analyzed the position and width of four secondary contact zones along three independent transects in the region of the Alps using maternally (mitochondrial DNA) and paternally (Y-chromosome) inherited genetic markers. Given male-biased dispersal in the common vole, a selectively neutral secondary contact would show broader paternal marker clines than maternal ones. In a selective case, for example, involving a form of Haldane’s rule, Y-chromosomal clines would not be expected to be broader than maternal markers because they are transmitted by the heterogametic sex and thus gene flow would be restricted. Consistent with the selective case, paternal clines were significantly narrower or at most equal in width to maternal clines in all contact zones. In addition, analyses using maximum likelihood cline-fitting detected a shift of paternal relative to maternal clines in three of four contact zones. These patterns suggest that processes at the contact zones in the common vole are not selectively neutral, and that partial reproductive isolation is already established between these evolutionary lineages. We conclude that hybrid zone movement, sexual selection and/or genetic incompatibilities are likely associated with an unusual unidirectional manifestation of Haldane’s rule in this common European mammal.

A day in the life of PubMed: analysis of a typical day's query log.

OBJECTIVE: To characterize PubMed usage over a typical day and compare it to previous studies of user behavior on Web search engines. DESIGN: We performed a lexical and semantic analysis of 2,689,166 queries issued on PubMed over 24 consecutive hours on a typical day. MEASUREMENTS: We measured the number of queries, number of distinct users, queries per user, terms per query, common terms, Boolean operator use, common phrases, result set size, MeSH categories, used semantic measurements to group queries into sessions, and studied the addition and removal of terms from consecutive queries to gauge search strategies. RESULTS: The size of the result sets from a sample of queries showed a bimodal distribution, with peaks at approximately 3 and 100 results, suggesting that a large group of queries was tightly focused and another was broad. Like Web search engine sessions, most PubMed sessions consisted of a single query. However, PubMed queries contained more terms. CONCLUSION: PubMed's usage profile should be considered when educating users, building user interfaces, and developing future biomedical information retrieval systems.

Within-winter movements: a common phenomenon in the Common Pochard Aythya ferina

Waterbirds are often observed to move between different wintering sites within the same winter—for example, in response to food availability or weather conditions. Within-winter movements may contribute to the spreading of diseases, such as avian influenza, outside the actual migration period. The Common Pochard Aythya ferina seems to be particularly sensitive to infection with the highly pathogenic avian influenza virus H5N1 and, consequently, could play an important role as vectors for the disease. We describe here the within-winter movements of Pochards in Europe in relation to topography, climate, sex and age. We analysed data provided by the Euring data bank on 201 individuals for which records from different locations from the same winter (December–February) were available. The distances and directions moved within the winter varied markedly between regions, which could be ascribed to the differing topography (coast lines, Alps). We found no significant differences in terms of distances and directions moved between the sexes and only weak indications of differences between the age classes. In Switzerland, juveniles moved in more westerly directions than adults. During relatively mild winters, winter harshness had no effect on the distances travelled, but in cold winters, a positive relationship was observed, a pattern possibly triggered by the freezing of lakes. Winter harshness did not influence the directions of the movement. About 41% (83/201) of the Pochards that were recovered at least 1 km from the ringing site had moved more than 200 km. A substantial number of birds moved between central/southern Europe and the north-western coast of mainland Europe, and between the north-western coast of mainland Europe and Great Britain, whereas no direct exchange between Great Britain and central/southern Europe was observed. Within-winter movements of Pochards seem to be a common phenomenon in all years and possibly occur as a response to the depletion of food resources. This high tendency to move could potentially contribute to the spread of bird-transmitted diseases outside the actual migration period.

Individual and spousal education, mortality and life expectancy in Switzerland: a national cohort study.

BACKGROUND Household measures of socioeconomic position may better account for the shared nature of material resources, lifestyle, and social position of cohabiting persons, but household measures of education are rarely used. We aimed to evaluate the association of combined educational attainment of married couples on mortality and life expectancy in Switzerland. METHODS The study included 3 496 163 ever-married persons aged ≥30 years. The 2000 census was linked to mortality records through 2008. Mortality by combined educational attainment was assessed by gender-age-specific HRs, with 95% CIs from adjusted models, life expectancy was derived using abridged life tables. RESULTS Having a less educated partner was associated with increased mortality. For example, the HR comparing men aged 50-64 years with tertiary education married to women with tertiary education to men with compulsory education married to women with compulsory education was 2.05 (1.92-2.18). The estimated remaining life expectancy in tertiary educated men aged 30 years married to women with tertiary education was 4.6 years longer than in men with compulsory education married to women with compulsory education. The gradient based on individual education was less steep: the HR comparing men aged 50-64 years with tertiary education with men with compulsory education was 1.74 (1.67-1.81). CONCLUSIONS Using individual educational attainment of married persons is common in epidemiological research, but may underestimate the combined effect of education on mortality and life expectancy. These findings are relevant to epidemiologic studies examining socio-demographic characteristics or aiming to adjust results for these characteristics.

Suitability of Common Collagen Scaffolds for Anterior Cruciate Ligament Repair

Introduction: Anterior cruciate ligament (ACL) injuries are very common; in Germany incidence of ACL ruptures is estimated at 32 per 100 000 in the general population and in the sports community this rate more than doubles. Current gold standard for anterior cruciate lig- ament repair is reconstruction using an autograft [1]. However, this approach has shown some limitations. A new method has been her- alded by the Knee Team at the Bern University Hospital (Inselspital) and the Sonnenhof clinic called Dynamic Intraligamentary Stabilization (DIS), which keeps ACL remnants in place in order to promote biologi- cal healing and makes use of a dynamic screw system [2]. The aim of this study was to investigate the cytocompatibility of collagen patches in combination with DIS to support regeneration of the ACL. The spe- cific hypothesis we tested was whether MSCs would differentiate towards TCs in co-culture. Materials and methods: Primary Tenocytes (TCs) and human bone marrow derived mesenchymal stem cells (MSCs) were harvested from ACL removed during knee prothesis or from bone marrow aspirations (Ethical Permit 187/10). Cells were seeded on two types of three dimensional carriers currently approved for cartilage repair, Novocart (NC, B. Brown) and Chondro-Gide (CG, Geistlich). These scaffolds comprise collagen structures with interconnecting pores originally developed for seeding of chondrocytes in the case of CG. ~40k cells were seeded on punched zylindrical cores of 8 mm in Ø and cultured on CG or NC patches for up to 7 days. The cells were either cultured as TC only, MSC only or co-cultured in a 1:1 mix on the scaffolds and on both sides of culture inserts (PET, high density pore Ø 0.4 mm, BD, Fal- con) with cell-cell contact. We monitored DNA content, GAG and HOP-content, tracked the cells using DIL and DIO fluorescent dyes (Molecular Probes, Life technologies) and confocal laser scanning and SEM microscopy as well as RT-PCR of tenocyte specific markers (i.e. col 1 and 3, TNC, TNMD, SCXA&B, and markers of dedifferentiation ACAN, col2, MMP3, MMP13). Finally, H&E stain was interpreted on cryosections and SEM images of cells on the scaffold were taken. Results: ThecLSMimagesshowedcellproliferationoverthe7dayson both matrices, however, on CG there were much fewer MSCs attached than on NC. SEM images showed a roundish chondrocyte-like pheno- type of cells on CG whereas on NC the phenotype was more teno- cyte-like (Fig. 1). Gene expression of both, MSC and TC seem to confirm a more favorable environment in 3D for both patches rather than monolayer control.

How common is the lipid body-containing interstitial cell in the mammalian lung?

Pulmonary lipofibroblasts are thought to be involved in lung development, regeneration, vitamin A storage, and surfactant synthesis. Most of the evidence for these important functions relies on mouse or rat studies. Therefore, the present study was designed to investigate the presence of lipofibroblasts in a variety of early postnatal and adult mammalian species (including humans) to evaluate the ability to generalize functions of this cell type for other species. For this purpose, lung samples from 14 adult mammalian species as well as from postnatal mice, rats, and humans were investigated using light and electron microscopic stereology to obtain the volume fraction and the total volume of lipid bodies. In adult animals, lipid bodies were observed only, but not in all rodents. In all other species, no lipofibroblasts were observed. In rodents, lipid body volume scaled with body mass with an exponent b = 0.73 in the power law equation. Lipid bodies were not observed in postnatal human lungs but showed a characteristic postnatal increase in mice and rats and persisted at a lower level in the adult animals. Among 14 mammalian species, lipofibroblasts were only observed in rodents. The great increase in lipid body volume during early postnatal development of the mouse lung confirms the special role of lipofibroblasts during rodent lung development. It is evident that the cellular functions of pulmonary lipofibroblasts cannot be transferred easily from rodents to other species, in particular humans.

Variation in life-history traits and their plasticities to elevational transplantation among seed families suggests potential for adaptative evolution of 15 tropical plant species to climate change

• Premise of the study: Because not all plant species will be able to move in response to global warming, adaptive evolution matters largely for plant persistence. As prerequisites for adaptive evolution, genetic variation in and selection on phenotypic traits are needed, but these aspects have not been studied in tropical species. We studied how plants respond to transplantation to different elevations on Mt. Kilimanjaro, Tanzania, and whether there is quantitative genetic (among-seed family) variation in and selection on life-history traits and their phenotypic plasticity to the different environments. • Methods: We reciprocally transplanted seed families of 15 common tropical, herbaceous species of the montane and savanna vegetation zone at Mt. Kilimanjaro to a watered experimental garden in the montane (1450 m) and in the savanna (880 m) zone at the mountain’s slope and measured performance, reproductive, and phenological traits. • Results: Plants generally performed worse in the savanna garden, indicating that the savanna climate was more stressful and thus that plants may suffer from future climate warming. We found significant quantitative genetic variation in all measured performance and reproductive traits in both gardens and for several measures of phenotypic plasticity in response to elevational transplantation. Moreover, we found positive selection on traits at low and intermediate trait values levelling to neutral or negative selection at high values. • Conclusions: We conclude that common plants at Mt. Kilimanjaro express quantitative genetic variation in fitness-relevant traits and in their plasticities, suggesting potential to adapt evolutionarily to future climate warming and increased temperature variability.

Neural correlates of wishful thinking.

Wishful thinking (WT) implies the overestimation of the likelihood of desirable events. It occurs for outcomes of personal interest, but also for events of interest to others we like. We investigated whether WT is grounded on low-level selective attention or on higher level cognitive processes including differential weighting of evidence or response formation. Participants in our MRI study predicted the likelihood that their favorite or least favorite team would win a football game. Consistent with expectations, favorite team trials were characterized by higher winning odds. Our data demonstrated activity in a cluster comprising parts of the left inferior occipital and fusiform gyri to distinguish between favorite and least favorite team trials. More importantly, functional connectivities of this cluster with the human reward system were specifically involved in the type of WT investigated in our study, thus supporting the idea of an attention bias generating WT. Prefrontal cortex activity also distinguished between the two teams. However, activity in this region and its functional connectivities with the human reward system were altogether unrelated to the degree of WT reflected in the participants' behavior and may rather be related to social identification, ensuring the affective context necessary for WT to arise.

Structure and dynamics of hybrid zones at different stages of speciation in the common vole (Microtus arvalis)

The genetic structure and dynamics of hybrid zones provide crucial information for understanding the processes and mechanisms of evolutionary divergence and speciation. In general, higher levels of evolutionary divergence between taxa are more likely to be associated with reproductive isolation and may result in suppressed or strongly restricted hybridization. In this study, we examined two secondary contact zones between three deep evolutionary lineages in the common vole (Microtus arvalis). Differences in divergence times between the lineages can shed light on different stages of reproductive isolation and thus provide information on the ongoing speciation process in M. arvalis. We examined more than 800 individuals for mitochondrial (mtDNA), Y-chromosome and autosomal markers and used assignment and cline analysis methods to characterize the extent and direction of gene flow in the contact zones. Introgression of both autosomal and mtDNA markers in a relatively broad area of admixture indicates selectively neutral hybridization between the least-divergent lineages (Central and Eastern) without evidence for partial reproductive isolation. In contrast, a very narrow area of hybridization, shifts in marker clines and the quasi-absence of Y-chromosome introgression support a moving hybrid zone and unidirectional selection against male hybrids between the lineages with older divergence (Central and Western). Data from a replicate transect further support non-neutral processes in this hybrid zone and also suggest a role for landscape history in the movement and shaping of geneflow profiles.

The changing pace of insular life: 5000 years of microevolution in the Orkney vole (Microtus arvalis orcadensis)

Island evolution may be expected to involve fast initial morphological divergence followed by stasis. We tested this model using the dental phenotype of modern and ancient common voles (Microtus arvalis), introduced onto the Orkney archipelago (Scotland) from continental Europe some 5000 years ago. First, we investigated phenotypic divergence of Orkney and continental European populations and assessed climatic influences. Second, phenotypic differentiation among Orkney populations was tested against geography, time, and neutral genetic patterns. Finally, we examined evolutionary change along a time series for the Orkney Mainland. Molar gigantism and anterior-lobe hypertrophy evolved rapidly in Orkney voles following introduction, without any transitional forms detected. Founder events and adaptation appear to explain this initial rapid evolution. Idiosyncrasy in dental features among different island populations of Orkney voles is also likely the result of local founder events following Neolithic translocation around the archipelago. However, against our initial expectations, a second marked phenotypic shift occurred between the 4th and 12th centuries AD, associated with increased pastoral farming and introduction of competitors (mice and rats) and terrestrial predators (foxes and cats). These results indicate that human agency can generate a more complex pattern of morphological evolution than might be expected in island rodents.