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The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed by computational detection tools. During the last decade, a plethora of such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools were used and detected over 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were empirically validated using three orthogonal methods. Generally, tool-specific precision values are high and similar (median of 98.8%, 96.3%, and 95.5% for qPCR, RNase R, and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant tool differentiators. Furthermore, we demonstrate the complementarity of tools through the increase in detection sensitivity by considering the union of highly-precise tool combinations while keeping the number of false discoveries low. Finally, based on the benchmarking results, recommendations are put forward for circRNA detection and validation.

Stable isotope signatures of domesticates found on archaeology sites provide information about past human behaviour, such as the evolution and adaptation of husbandry strategies. A dynamic phase in cattle husbandry evolution is during the 6th millennium BCE, where the first cattle herders of central Europe spread rapidly through diverse forested ecological niches, where little is known about pasturing strategies. Here we investigate cattle pasturing and foddering practices using a multi-regional dataset of stable isotope values (δ13C and δ18O; compound-specific stable isotopic analysis δ15N-amino acids and δ13C-dairy fats) measured from cattle bone and teeth, and pottery residues from early farming contexts, and palaeoenvironmental information. Our analysis reveals that farmers practiced different pasturing strategies with the intensive use of forested ecosystems in some areas for both graze and seasonal forage. We propose that the diversity of strategies is related to the adaptation of herding to new environments, which had a positive impact on cattle breeding and milk availability for human consumption.

Genome size in the rotifer Brachionus asplanchnoidis, which belongs to the B. plicatilis species complex, is greatly enlarged and extremely variable (205–407 Mbp). Such variation raises the question whether large genome size differences among individuals might cause reproductive barriers, which could trigger speciation within this group by restricting gene flow across populations. To test this hypothesis, we used B. asplanchnoidis clones from three geographic populations and conducted assays to quantify reproductive isolation among clones differing in genome size, and we examined the population structure of all three populations using amplified fragment length polymorphisms (AFLPs). AFLPs indicated that these populations were genetically separated, but we also found hints of natural gene flow. Clones from different populations with genome size differences of up to 1.7-fold could interbred successfully in the laboratory and give rise to viable, fertile ‘hybrid’ offspring. Genome sizes of these ‘hybrids’ were intermediate between those of their parents, and fitness in terms of male production, population growth, and egg development time was not negatively affected. Thus, we found no evidence for reproductive isolation or nascent speciation within B. asplanchnoidis. Instead, our results suggest that gene flow within this species can occur despite a remarkably large range of genome sizes.

The Danube region in Central Europe was one of the areas where several cultures appeared before moving further or being defeated during the Migration Period in the middle of the first millennium AD. The Lombards, who crossed the Danube in 505 AD, settled in the “Tullnerfeld” where the Maria Ponsee graveyard was excavated in 1965–1972. From the historical evidence about the temporal and spatial migration of the Lombards, it was concluded that the graveyard was in use between 505 and 568 AD by three groups of migrants. We processed and dated a new set of 23 bones, found in the Maria Ponsee site. The determined 14C dates fit well in the expected time interval, though discrimination between the grave groups could not be obtained. The dates were added to the chronological sequence, recording the Migration Period in Central Europe. The sequence lead to a good correlation of the modelled and historical data (Amodel = 87.6%). The results show differentiations of the respective tribes in the pre-Lombardic period. However, transitions between the Lombard phases were rather ambiguous, indicating that the Lombards set up new settlements while only partially abandoning the already inhabited ones before 546 AD.

We can shorten any path that links two given points by applying short ruler transforms iteratively. In this article we take a closer look at a short ruler process on the torus. The torus is a compa...

The Linear Pottery people in 5670-5000 BC at the Brunn sites in Austria produced birch and beech bark pitches. Big globular vessels and closed high bowls could have been containers for the production and storage of this substance. Miniature vessels with a handle for hanging had contained small portions. Bark pitch as an adhesive for the repair of pottery and in the construction of big idols is also testified, as is the application of this material in decoration of vessels and idols, where bark pitch was a matrix for inlaying with grains or stones and creation of a contrasting black colour in linear ornamentation. Radiocarbon dating of bark pitch now is one of the most reliable materials for age determination of the Neolithic objects.

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation—proxies for these drivers—provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

We describe a synthetic riboswitch element that implements a regulatory principle which directly addresses an essential tRNA maturation step. Constructed using a rational in silico design approach, this riboswitch regulates RNase P-catalyzed tRNA 5′-processing by either sequestering or exposing the single-stranded 5′-leader region of the tRNA precursor in response to a ligand. A single base pair in the 5′-leader defines the regulatory potential of the riboswitch both in vitro and in vivo. Our data provide proof for prior postulates on the importance of the structure of the leader region for tRNA maturation. We demonstrate that computational predictions of ligand-dependent structural rearrangements can address individual maturation steps of stable non-coding RNAs, thus making them amenable as promising target for regulatory devices that can be used as functional building blocks in synthetic biology.

Aus dem Awarenreich sind einige wenige Glockenfunde bekannt, die jedoch nicht weiter erforscht sind. Um Aufschluss uber ihre Funktion und Bedeutung zu erhalten, wurden in einer Pilotstudie funf Bronzeglockchen aus dem spatawarischen Madchengrab 157, Vosendorf- Laxenburger Strase, Niederosterreich, auf Tonhohe, Schallpegel und Reichweite akustisch untersucht. Die Grundtone der beiden groseren und eines der drei kleinen Glockchen ergaben einen Dreiklang, welcher durch das vierte gemessene kleine Glockchen durch eine Sekund gestort wurde. Der Schallpegel der Glockchen ist gering, ihre Reichweite geht nicht uber 0,5 m hinaus. Die im zweiten Teil des Beitrags vorgestellte Glockentypologie zeigt, dass die Formen Grosteils antike Wurzeln haben, drei Typen durften auf ostliche Vorganger zuruckgehen. Alle 72 bislang bekannten awarischen Glocken, die aus 40 Fundorten und 63 Fundkontexten stammen, beschranken sich auf Ungarn, Osterreich, Serbien und die Slowakei. Zurzeit sind keine Funde aus Rumanien bekannt. Ist in fruhawarischer Zeit die groste Anzahl an Glocken in Gebrauch, so nimmt diese in den spateren Epochen rapide ab, was wahrscheinlich darauf zuruckzufuhren ist, dass Schellen modern werden. Der Vergleich der Glockenfunde aus den 53 Awarengrabern bezuglich ihrer Lage im Grab zeigt, dass sich die meisten Glocken im Becken- und Oberschenkelbereich befanden. Das deutet darauf hin, dass die Idiophone in Behaltnissen oder an Ketten bzw. Schnuren am Gurtel getragen wurden. Der Brauch, sich mit Glocken zu schmucken bzw. diese mit sich herumzutragen, durfte vorwiegend spatantike Wurzeln haben und steht moglicherweise mit apotropaischem Schutz in Verbindung. Innerhalb der Graber mit Glocken nehmen Frauenbestattungen die erste Stelle ein, gefolgt von Kindern und Mannern. Lediglich in einem Grab lag die Glocke beim Pferd. Da in der Regel jedes Grab nur eine Glocke enthielt, nehmen das Madchengrab 157 aus Vosendorf-Laxenburger Strase mit funf Bronzeglockchen, das Mannergrab 471 aus Kolked Feketekapu A mit drei Eisenglocken und drei weitere ungarische Graber mit je zwei Glocken eine Ausnahmestellung ein.

On complete Riemannian manifolds, a geodesic linking two different points could be approximated by applying short ruler methods to shorten a given path iteratively. In this paper we take a closer look at a short ruler method on a cone. To handle the problems caused by the fact that the cone is not smooth at its apex, we unwind the cone isometrically into the plane, and show that the sequence of shortened curves converges to a geodesic.

Within-species variation in genome size has been documented in many animals and plants. Despite its importance for understanding eukaryotic genome diversity, there is only sparse knowledge about how individual-level processes mediate genome size variation in populations. Here we study a natural population of the rotifer Brachionus asplanchnoidis whose members differ up to 1.9-fold in genome size, but were still able to interbreed and produce viable offspring. We show that genome size is highly heritable and can be artificially selected up or down, but not beyond a minimum diploid genome size. Analyses of segregation patterns in haploid males reveal that large genomic elements (several megabases in size) provide the substrate of genome size variation. These elements, and their segregation patterns, explain the generation of new genome size variants, the short-term evolutionary potential of genome size change in populations, and some seemingly paradoxical patterns, like an increase in genome size variation among highly inbred lines. Our study suggests that a conceptual model involving only two variables, (1) a minimum genome size of the population, and (2) a vector containing information on additional elements that may increase genome size in this population (size, number, and meiotic segregation behaviour), can effectively address most scenarios of short-term evolutionary change of genome size in a population.

Archaeogenetic research over the last decade has demonstrated that European Neolithic farmers (ENFs) were descended primarily from Anatolian Neolithic farmers (ANFs). ENFs, including early Neolithic central European Linearbandkeramik (LBK) farming communities, also harbored ancestry from European Mesolithic hunter gatherers (WHGs) to varying extents, reflecting admixture between ENFs and WHGs. However, the timing and other details of this process are still imperfectly understood. In this report, we provide a bioarchaeological analysis of three individuals interred at the Brunn 2 site of the Brunn am Gebirge-Wolfholz archeological complex, one of the oldest LBK sites in central Europe. Two of the individuals had a mixture of WHG-related and ANF-related ancestry, one of them with approximately 50% of each, while the third individual had approximately all ANF-related ancestry. Stable carbon and nitrogen isotope ratios for all three individuals were within the range of variation reflecting diets of other Neolithic agrarian populations. Strontium isotope analysis revealed that the ~50% WHG-ANF individual was non-local to the Brunn 2 area. Overall, our data indicate interbreeding between incoming farmers, whose ancestors ultimately came from western Anatolia, and local HGs, starting within the first few generations of the arrival of the former in central Europe, as well as highlighting the integrative nature and composition of the early LBK communities.

Significance The first historically reported pandemic attributed to Yersinia pestis started with the Justinianic Plague (541–544) and continued for around 200 y as the so-called First Pandemic. To date, only one Y. pestis strain from this pandemic has been reconstructed using ancient DNA. In this study, we present eight genomes from Britain, France, Germany, and Spain, demonstrating the geographic range of plague during the First Pandemic and showing microdiversity in the Early Medieval Period. Moreover, we detect similar genome decay during the First and Second Pandemics (14th to 18th century) that includes the same two virulence factors, thus providing an example of potential convergent evolution of Y. pestis during large-scale epidemics., The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium’s spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymorphisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic.

Magnetic resonance imaging and the correlation to histopathological findings of the equine palmar foot of lame horses have been described previously, using 0.27 and 1.5 T systems. Compared to these, 3 T systems provide superior spatial resolution and imaging contrast. The aim of our prospective anatomic study was to characterize the imaging anatomy of the navicular region on 3 T MRI in comparison to histopathological findings. We hypothesized that 3 T MRI allows a good visualization of the entire navicular apparatus and reliable measurements of navicular cartilage and cortical bone thickness. Twenty front feet of sound horses were examined using a 3 T MRI system. For histopathological examination, sagittal tissue sections of the navicular bones and adjacent ligaments were prepared. Alterations in magnetic resonance signal were graded for each region and compared to corresponding histological slices. Overall, there was good visualization of the anatomical detail and a very good agreement between MRI and histology for compact bone and spongiosa, good agreement for the fibrocartilage and the distal sesamoidean impar ligament, but only moderate agreement for the hyaline cartilage and the collateral sesamoidean ligament. A comparative measurement of cartilage and cortical bone thickness on magnetic resonance images and histological sections was performed. In MRI, the hyaline cartilage of the articular surface appeared significantly thinner and the fibrocartilage of the flexor surface appeared significantly thicker compared to histology. Findings indicated that MRI at a field strength of 3 T allows reliable depiction of anatomic details of the navicular apparatus.

Genome size in the rotifer Brachionus asplanchnoidis, which belongs to the B. plicatilis species complex, is greatly enlarged and extremely variable (205–407 Mbp). Such variation raises the question whether large genome size differences among individuals might cause reproductive barriers, which could trigger speciation within this group by restricting gene flow across populations. To test this hypothesis, we used B. asplanchnoidis clones from three geographic populations and conducted assays to quantify reproductive isolation among clones differing in genome size, and we examined the population structure of all three populations using amplified fragment length polymorphisms (AFLPs). AFLPs indicated that these populations were genetically separated, but we also found hints of natural gene flow. Clones from different populations with genome size differences of up to 1.7-fold could interbred successfully in the laboratory and give rise to viable, fertile ‘hybrid’ offspring. Genome sizes of these ‘hybrids’ were intermediate between those of their parents, and fitness in terms of male production, population growth, and egg development time was not negatively affected. Thus, we found no evidence for reproductive isolation or nascent speciation within B. asplanchnoidis. Instead, our results suggest that gene flow within this species can occur despite a remarkably large range of genome sizes.

Stress wird gemas verschiedenen wissenschaftlichen Ansatzen als Reaktion von Menschen auf Stressoren betrachtet. Andererseits werden aber auch Stressoren selbst verschiedentlich als „Stress“ bezeichnet. Dieses Kapitel beleuchtet – unabhangig von Nomenklaturen – physiologische und psychologische, lang- und kurzfristige Stressreaktionen. Als Beispiel fur eine langerfristige Stressreaktion wird das Burn-out-Syndrom dargestellt.

Die Person einerseits und die Situation andererseits konnen Merkmale aufweisen, die die negative Wirkung von Stressoren abpuffern und somit der Entstehung von Stress entgegenwirken. Soziale Unterstutzung ist eines dieser Merkmale. Im Folgenden werden analog zur Darstellung der Stressoren verschiedene Ressourcen aus der Person, der arbeitsbezogenen Rolle, dem sozialen Umfeld, dem Behavior Setting („Verhaltensraum“), der physikalisch-technologischen Umwelt, der Aufgabe, der Organisation sowie der Kultur beschrieben. Wir gehen insbesondere auf die Rolle der sozialen Unterstutzung ein, da diese eine zentrale Ressource gegen Stress darstellt.

Im Folgenden werden Beispiele fur Gefahrdungsbeurteilungen – „good practices“ – aus der Praxis groser, kleiner und mittelstandischer Unternehmen sowie aus dem offentlichen Dienst beschrieben.

In diesem Kapitel werden die rechtlichen Grundlagen der Gefahrdungsbeurteilung dargestellt sowie die Vorgehensweisen und Probleme bei der psychischen Gefahrdungsbeurteilung. Abschliesend geben wir Empfehlungen fur eine erfolgreiche Umsetzung.

In recent decades, an increasing number of studies have aimed to shed light on the origin and spread of tuberculosis in past human populations. Here we present the results of a systematic palaeodemographic and palaeopathological survey of the Early Mediaeval population of Gars/Thunau (Lower Austria), which - at this stage - includes 373 individuals recovered at two archaeological sub-sites: a fortified settlement (including a necropolis) at the top of a hill - probably reserved for social and military elites; and a large riverine settlement at the foot of the hill, a so-called 'suburbium', where burials and an area of 'industrial' character were discovered. We recorded a great number of pathological alterations and a variety of 'classical' features of tuberculosis, such as vertebral destructions (Pott's disease) and joint destructions, and other pathological (unspecific) features probably linked with Mycobacterium tuberculosis infection (e.g. new bone formation at the inner surface of the ribs, endocranial alterations in the form of 'pits', and new bone formation at the cranial base). We hypothesize that the two contemporaneous (∼900-1000 AD) populations of Gars/Thunau differed not only in their social affiliation/condition, but also in the type and frequencies of their population-density-related infectious diseases (in particular tuberculosis). Moreover, we investigated the molecular genetic evidence of the causative organism in a few selected immatures exhibiting pathological changes at the inner wall of the cranium and discuss these findings in regard to the macroscopic features observed. Finally, we analysed carbon and nitrogen stable isotopes of both populations and strontium isotope ratios of the hill-top inhabitants in order to reconstruct certain aspects of diet and mobility to test our hypothesis concerning the specific social and/or military character of the site.

On a Lie group G, the restrictions of a homomorphism h:(R,+)→(G,∘) to intervals [a,b] are geodesic according to the left- or right-invariant connection. If this affine connection is torsion free, G is a Riemannian manifold. On Riemannian manifolds in general, it's difficult to compute geodesics (i.e. locally shortest lines) between two points, which are far away from each other. But any curve connecting the two points can be shortened by using a ruler, which allows to construct short geodesics:In normed vector spaces, we look at the midpoint method and the reduced method, which shorten the curve iterative. Both let converge a curve to the geodesic: the straight line between starting point and end point of the curve. On Riemannian manifolds, we get a weaker result: The reduced method can be generalized to complete Riemannian manifolds and on some of them – as for example the hyperbolic spaces – the reduced method lets converge each curve to a geodesic between its starting point and end point.

Summary The horse frequently shows idiopathic primary lymphoedema or secondary lymphoedema following trauma or infection to its limbs. Lymphoedema develops if the balance between the amount of lymphatic fluid and capacity of lymphatic transport is disturbed. Scintigraphy appears to be the only in vivo technique to evaluate lymphatic transport capacity. The aim of this study was to develop an evaluation technique to determine the lymph flow in the hindlimb of the horse. This technique might show potential to extend the possibilities for investigating disorders of the lymphatic system in equine extremities.

International audience; The paper provides an overview of and an update on the on-going proposal to create a component within the TEI architecture. It elicits the conceptual background of having stand-off annotations embedded within a TEI document and the consequences in terms of primary source preservation, multiple annotation views and possible exporting of annotation content into autonomous TEI documents. It demonstrates the various types of possible use cases ranging from manual annotation to fully automatized information extraction processes and show the importance of implementing, right from the onset, the possibility to use any kind of internal or external vocabulary for representing annotation bodies (e.g. to deal with structural or conceptual annotations). An important prospect here is that the construct could lead to a simplified development of TEI-aware online services such as Named Entity Recognisers.We relate to on-going initiatives and show the necessity to align with the Web Annotation Data Model (W3C) as well as with the recent introduction of the element for speech transcription (as part of the work carried out in the ISO standard 24624) as an elementary annotation crystal in the sense of Romary and Wegstein (2012). In this context we tackle the issue of implicitness in the representation of annotations and open the debate related to the trade-off between having a terse vs. highly flexible model.We end up by illustrating the application that is already made of the current proposal in various projects related to data mining or scientific information, and in particular to the representation of annotated scholarly content.Further materials•Minutes of the January 2014 meeting: http://download2.polytechnic.edu.na/pub7/sourceforge/l/li/lingsig/Documents/Standoff%20in%20Berlin,%2001.2014/standoff-minutesBerlin2014.pdf•The TEI GitHub ticket: https://github.com/TEIC/TEI/issues/374 •The standOff proposal on GitHub: https://github.com/laurentromary/stdfSpec (branch AnnArbor)ReferencesBański Piotr (2010). Why TEI standoff annotation doesn’t quite work: and why you might want to use it nevertheless. In Proceedings of Balisage: The Markup Conference, 2010. Vol. 5 of Balisage Series on Markup Technologies ISO/DIS 24624 Language resource management -- Transcription of spoken languagePose Javier, Patrice Lopez and Laurent Romary (2014). A Generic Formalism for Encoding Stand-off annotations in TEI. 2014. Romary Laurent (2015). TEI challenges in an accelerating digital world. DiXiT Convention week, Sep 2015, The Hague, Netherlands. 2015, . Romary Laurent and Werner Wegstein (2012), « Consistent Modeling of Heterogeneous Lexical Structures », Journal of the Text Encoding Initiative [Online], Issue 3 | November 2012, Online since 15 October 2012, connection on 12 May 2016. URL : http://jtei.revues.org/540 ; DOI : 10.4000/jtei.540 (section about Crystals : https://jtei.revues.org/540#tocfrom2n1)Web Annotation Data Model, W3C, https://www.w3.org/TR/annotation-model/