Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic.

The Black Death (1347-1352 CE) is the most renowned pandemic in human history, believed by many to have killed half of Europe's population. However, despite advances in ancient DNA research that conclusively identified the pandemic's causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, 'big data palaeoecology', which, starting from palynological data, evaluates the scale of the Black Death's mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death's mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics.

Challenges and perspectives of computer-assisted instruction in medical education: lessons learned from seven years of experience with the CAMPUS system.

OBJECTIVES: In this paper we discuss solutions to the problem that medical teachers and students do not use modern computer-assisted instruction systems in medical education as much as expected by their developers. METHODS: As an example for a modern problem-based CAI system we introduce the CAMPUS shell system for case-based training in medicine. RESULTS: CAMPUS has received several awards and positive evaluation results. Nevertheless, the usage of such systems in courses and for self-study could be increased. CONCLUSIONS: Curricular integration of CAI as well as further improvements on existing CAI systems to increase the usage in medical education is essential.

[Computer-assisted system for analysis of heart rate variability in clinical studies]. / Ein Computergestütztes System zur Analyse der Herzfrequenzvariabilität im Rahmen klinischer Studien.

This paper describes an adaptable framework that facilitates exploratory analysis, interpretation and classification of beat-to-beat data extracted from the electrocardiogram (ECG). The system supports a variety of user-defined annotations and allows the definition of analysis programs. Special care is taken on the correct treatment of corrupted and missing data, ubiquitously found in real world problems. Besides the computation, the performance of single features can be inspected using different kinds of diagrams provided by the system. Combinations of features can be evaluated using a polynomial classifier. Both the computation and combination of features are defined as tasks that can be dispatched by a server to various clients. The framework is easily adaptable to different problem structures and has been used successfully in three studies.

Dynamic analyses of the expression of the HISTONE::YFP fusion protein in arabidopsis show that syncytial endosperm is divided in mitotic domains.

During early seed development, nuclear divisions in the endosperm are not followed by cell division, leading to the development of a syncytium. The simple organization of the Arabidopsis endosperm provides a model in which to study the regulation of the cell cycle in relation to development. To monitor nuclear divisions, we constructed a HISTONE 2B::YELLOW FLUORESCENT PROTEIN gene fusion (H2B::YFP). To validate its use as a vital marker for chromatin in plants, H2B::YFP was expressed constitutively in Arabidopsis. This enabled the observation of mitoses in living root meristems. H2B::YFP was expressed specifically in Arabidopsis syncytial endosperm by using GAL4 transactivation. Monitoring mitotic activity in living syncytial endosperm showed that the syncytium was organized into three domains in which nuclei divide simultaneously with a specific time course. Each mitotic domain has a distinct spatiotemporal pattern of mitotic CYCLIN B1;1 accumulation. The polar spatial organization of the three mitotic domains suggests interactions between developmental mechanisms and the regulation of the cell cycle.

Adaptations for rapid and forceful contraction in wing muscles of the male golden-collared manakin: sex and species comparisons.

The courtship display of the male golden-collared manakin (Manacus vitellinus) of Panamanian rainforests is noteworthy for several types of whip-crack-like sounds created by a rapid overhead flip of the wings. We have hypothesized that this courtship behavior. which is not performed by females, is associated with steroid-sensitive and sexually dimorphic neuromuscular systems. Presumably, muscles creating the motion of the wingsnap in males are specialized for greater force generation and speed of contraction. We tested this hypothesis by examining mass, fiber diameter, metabolic enzyme activity, and myosin isoform expression in several muscles of male and female manakins and in both sexes of a non-wingsnapping bird, the zebra finch (Taenopygia guttata). We have identified three wing muscles, the scapulohumeralis caudalis, the supracoracoideus, and the pectoralis major, that differ in one or more of these characteristics across sex and species, suggesting they are specialized for faster contraction and greater force production in male manakins. These muscles normally function to raise and lower the wings during flight. As this movement is the principal motion of the wingsnap, these adaptations presumably underlie the performance of the wingsnap display.

Axially chiral amidinium ions as inducers of enantioselectivity in Diels-Alder reactions

[reaction: see text] Enantioselective catalysis of Diels-Alder reactions is mostly achieved by coordinating the dienophile to relatively strong chiral Lewis acids. Here we report on a novel approach employing the hydrogen-bond-mediated association of dienophiles to chiral host molecules. In a reaction forming the steroid skeleton of norgestrel, chiral amidinium ions induce 5:ent-5 ratios of up to 2.5:1. Improved and simplified amidinium catalysts may become interesting candidates to perform stereoselective transformations.

Constitution and solution conformation of the antibiotic mersacidin determined by NMR and molecular dynamics.

The solution structure of the tetracyclic lantibiotic mersacidin in methanol (CD3OH) has been determined by NMR followed by distance bound driven dynamics and subsequent restrained molecular dynamics simulations combined with an iterative relaxation matrix approach and alternatively by a simulated annealing protocol. The molecular dynamics simulations were performed with the AMBER program system and with the INSIGHT program package. The distance bound driven dynamics calculation was conducted using a modified version of the DISGEO II program. The interproton distance restraints were derived from jump symmetrized rotating-frame Overhauser enhancement and exchange (JS-ROESY) spectra, which yield optimum sensitivity for medium-sized molecules like mersacidin. The connectivities via the sulfide bridges were unambiguously confirmed by heteronuclear NMR techniques (heteronuclear single quantum coherence and heteronuclear multiple bond correlation methods). Due to the tetracyclic structure, mersacidin exhibits a rather rigid globular shape, which neither belongs to the duramycin nor to the nisin structure type lantibiotics. The resulting structures for the simulated annealing protocol of restrained and subsequent free molecular dynamics were compared and found to be very similar.

Atrial natriuretic peptide as a marker for doxorubicin-induced cardiotoxic effects.

Doxorubicin is an effective antineoplastic agent, but it frequently causes dose-related cardiotoxic effects. Because the atrial natriuretic peptide (ANP) level is elevated in children with heart defects, the authors measured the ANP levels in children to determine whether ANP might serve as a simple diagnostic indicator of cardiotoxic effects. Sixteen patients, 5 to 19 years of age, who were being treated with doxorubicin (45 mg/m2 body surface area) for various malignancies had ANP levels measured in plasma. There was a group of six children, with a significant peak of plasma ANP (pANP) levels 3 weeks after the administration of the drug. Of these six patients, five had received high cumulative doses of doxorubicin (160 to 370 mg/m2), and two of them went into congestive heart failure without a previous decline in left ventricular ejection fraction, a standard technique for monitoring cardiac function during treatment with doxorubicin. The other ten patients had normal ANP levels throughout the study, and signs of cardiac dysfunction did not develop. None of the patients in the control group who had cancer and were not treated with doxorubicin and none of the healthy volunteers had elevated ANP levels. These preliminary results suggest that pANP may be useful as an early and sensitive indicator for doxorubicin-related myocardial damage.