Spiral cleavage and early embryology of a loxosomatid entoproct and the usefulness of spiralian apical cross patterns for phylogenetic inferences

Background: Among the four major bilaterian clades, Deuterostomia, Acoelomorpha, Ecdysozoa, and Lophotrochozoa, the latter shows an astonishing diversity of bodyplans. While the largest lophotrochozoan assemblage, the Spiralia, which at least comprises Annelida, Mollusca, Entoprocta, Platyhelminthes, and Nemertea, show a spiral cleavage pattern, Ectoprocta, Brachiopoda and Phoronida (the Lophophorata) cleave radially. Despite a vast amount of recent molecular phylogenetic analyses, the interrelationships of lophotrochozoan phyla remain largely unresolved. Thereby, Entoprocta play a key role, because they have frequently been assigned to the Ectoprocta, despite their differently cleaving embryos. However, developmental data on entoprocts employing modern methods are virtually non-existent and the data available rely exclusively on sketch drawings, thus calling for thorough re-investigation. Results: By applying fluorescence staining in combination with confocal microscopy and 3D-imaging techniques, we analyzed early embryonic development of a basal loxosomatid entoproct. We found that cleavage is asynchronous, equal, and spiral. An apical rosette, typical for most spiralian embryos, is formed. We also identified two cross-like cellular arrangements that bear similarities to both, a "molluscan-like" as well as an "annelid-like" cross, respectively. Conclusions: A broad comparison of cleavage types and apical cross patterns across Lophotrochozoa shows high plasticity of these character sets and we therefore argue that these developmental traits should be treated and interpreted carefully when used for phylogenetic inferences

Writing against the odds : the south’s cultural and literary struggle against progress and modernity

Die Literatur und Kultur der Südstaaten ist entscheidend geprägt von ihrer Orientierung an der eigenen Geschichte und Vergangenheit. Die düstere Vergangenheit, die die Gegenwart überschatten und die Zukunft determiniert ist ein Südstaatenthema par exellence und allgegenwärtig in ihrer Kultur und Literatur. Nach dem Bürgerkrieg und der Reconstruction Era ist der Süden kulturell und ökonomisch ausgeblutet, am Boden und isoliert. Nach dem Krieg weitet sich die Kluft zwischen Nord- und Südstaaten immer weiter aus, ein Prozess, der jedoch schon so alt ist wie die Vereinigten Staaten selbst und bereits im beginnenden 18. Jahrhundert seinen Anfang nimmt. Die Isolation ist gleichzeitig gewollt und ungewollt, bewusst und unbewusst. Die Scham des verlorenen Krieges und die Marginalisierung sind die Katalysatoren für die Kultivierung und das Bestreben nach Erhalt der Besonderheiten der Südstaaten, mit ihrer vermeintlich überlegenen Kultur und Moral. Es beginnt die kommerzialisierte, hoch ideologisierte Konstruktion der Geschichte und Identität der Südstaaten, die in alle Lebensbereiche strahlt. Der melancholische Blick in die Vergangenheit als wichtigste Referenz und kulturellen Fluchtpunkt ersetzt den Eintritt in die Moderne und Modernität mit ihrer Schnelllebigkeit, Austauschbarkeit und die Aufgabe der Tradition für eine rasante Gegenwart. Das Individuum der Südstaaten sieht sich statt mit einer Flut an Wahlmöglichkeiten und Optionen, mit einer einengenden Gesellschaft konfrontiert, die wenig Spielraum für Abweichungen übriglässt und ein harsches Kontrollsystem hat. Es ist eine einzigartige Mischung aus Stolz, Scham und einem Gefühl der gleichzeitigen Unter- und Überlegenheit, die einen besonders guten literarischen Nährboden hervorbringt. In dieser Arbeit wird den historischen, kulturellen, und literarischen Wurzeln der Südstaatenliteratur seit der Southern Renaissance nachgegegangen, um dann die ständig perpetuierten formalen und inhaltlichen Strukturen darzustellen, die wenig Veränderungen erfahren haben. Diese Perpetuierung resultiert aus der einzigartigen Situation der Südstaaten, aus der historischen Last, die unvermindert aktuell bleibt und längst nicht verarbeitet ist. Südstaatenautoren konnten und können nicht die traditionellen Formen und Themen ablegen, solange diese konstituierende Bestandteile der Kultur und Identität der Südstaaten bleiben. Die Südstaaten verweigern sich der Modernität und empfinden Fortschritt und die moderne Massengesellschaft nicht nur als Bedrohung, sondern als Einfluss aus den Nordstaaten, der die eigene Kultur bedroht und eine Einmischung von außen ist, die es abzuwenden gilt. Traditionsbewusste, reaktionäre Tendenzen und Elemente ziehen sich selbst durch vermeintlich progressive, moderne Entwicklungen und Phänomene. Ich kombiniere identitätskonstituierende, isolierende und melancholische Elemente und beleuchte sie historisch, kulturell und literarisch, um eine mehrschichtige Perspektive zu erlangen. Das Verständnis dieser historischen Last und deren unverminderte Bedeutung und Auswirkung auf die Literatur und Kultur der Südstaaten ist essentiell für eine tiefere Einsicht in deren Strukturen und Bedeutung

Prospective comparison of nine different handheld ultrasound (HHUS) devices by ultrasound experts with regard to B-scan quality, device handling and software in abdominal sonography

The HHUS market is very complex due to a multitude of equipment variants and several different device manufacturers. Only a few studies have compared different HHUS devices under clinical conditions. We conducted a comprehensive prospective observer study with a direct comparison of nine different HHUS devices in terms of B-scan quality, device handling, and software features under abdominal imaging conditions. Methods: Nine different HHUS devices (Butterfly iQ+, Clarius C3HD3, D5CL Microvue, Philips Lumify, SonoEye Chison, SonoSite iViz, Mindray TE Air, GE Vscan Air, and Youkey Q7) were used in a prospective setting by a total of 12 experienced examiners on the same subjects in each case and then assessed using a detailed questionnaire regarding B-scan quality, handling, and usability of the software. The evaluation was carried out using a point scale (5 points: very good; 1 point: insufficient). Results: In the overall evaluation, Vscan Air and SonoEye Chison achieved the best ratings. They achieved nominal ratings between “good” (4 points) and “very good” (5 points). Both devices differed significantly (p < 0.01) from the other seven devices tested. Among the HHUS devices, Clarius C3HD3 and Vscan Air achieved the best results for B-mode quality, D5CL Microvue achieved the best results for device handling, and SonoEye Chison and Vscan Air achieved the best results for software. Conclusions: This is the first comprehensive study to directly compare different HHUS devices in a head-to-head manner. While the majority of the tested devices demonstrated satisfactory performance, notable discrepancies were observed between them. In particular, the B-scan quality exhibited considerable variation, which may have implications for the clinical application of HHUS. The findings of this study can assist in the selection of an appropriate HHUS device for specific applications, considering the clinical objectives and acknowledging the inherent limitations

Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.

Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+) and NPM-ALK-negative (ALK-) anaplastic large-cell lymphoma (ALCL). We find that ALK+ and ALK- ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we uncover a close relationship between global ALCL DNA methylation patterns and those in distinct thymic developmental stages and observe tumor-specific DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs such as AP1. Our results indicate similarity between ALCL tumor cells and thymic T cell subsets and a direct relationship between ALCL oncogenic signaling and DNA methylation through transcription factor induction and occupancy.G.E. was funded by the Austrian Science Foundation (FWF) (P 27616 and V 102). M.R.H. was supported by a L’Oréal for Women in Science grant. S.D.T. receives funding from Bloodwise (formerly Leukaemia and Lymphoma Research). L.K. has been funded by the FWF (P 26011 and P 29251), as well as the MSCA-ITN-2015-ETN ALKATRAS (No. 675712). D.J.W. is a paid consultant for Zymo Research Corporation.This is the final version of the article. It first appeared from Elsevier (Cell Press) via http://dx.doi.org/10.1016/j.celrep.2016.09.01

The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models

Arterial networks enlarge in response to increase in tissue metabolism to facilitate flow and nutrient delivery. Typically, the transition of a growing artery with a small diameter into a large caliber artery with a sizeable diameter occurs upon the blood flow driven change in number and shape of endothelial cells lining the arterial lumen. Here, using zebrafish embryos and endothelial cell models, we describe an alternative, flow independent model, involving enlargement of arterial endothelial cells, which results in the formation of large diameter arteries. Endothelial enlargement requires the GEF1 domain of the guanine nucleotide exchange factor Trio and activation of Rho-GTPases Rac1 and RhoG in the cell periphery, inducing F-actin cytoskeleton remodeling, myosin based tension at junction regions and focal adhesions. Activation of Trio in developing arteries in vivo involves precise titration of the Vegf signaling strength in the arterial wall, which is controlled by the soluble Vegf receptor Flt1. Arterial flow regulates artery diameter but other mechanisms may also affect this. Here, the authors show that the guanine nucleotide exchange factor Trio and GTPases Rac1 and RhoG, triggers F-actin remodeling in arterial endothelial cells, independent of flow, to enhance lumen diameter in zebrafish and cell models.Peer reviewe

Validation of the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis by disease content experts

The European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody-associated vasculitis have been recently published. Unique to recommendation development, they were also voted on by members of a learned society. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis. In addition to the task force, a learned society (European Vasculitis Society-EUVAS) was invited, through online survey, to rate independently the strength of evidence of each recommendation to obtain an indication of the agreement among the final target audience and ultimate end-users of the recommendations. The survey took place in June 2015. Of the 158 EUVAS members surveyed, there were 88 responses (55.7%). There was a large degree of agreement in the voting patterns between EUVAS survey participants and task force members. Notable exceptions were lower grades for the recommendation of the use of rituximab for remission induction in patients with eosinophilic granulomatosis with polyangiitis and for methotrexate and mycophenolate mofetil as remission maintenance agents in patients with granulomatosis with polyangiitis/microscopic polyangiitis by EUVAS members. These results are encouraging and suggest that the voting patterns of the task force are representative of the wider vasculitis community. We recommend future recommendations adopt this approach for data/expert-based treatment guidelines, especially for multisystem diseases

Validation of the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis by disease content experts.

The European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody-associated vasculitis have been recently published. Unique to recommendation development, they were also voted on by members of a learned society. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis. In addition to the task force, a learned society (European Vasculitis Society-EUVAS) was invited, through online survey, to rate independently the strength of evidence of each recommendation to obtain an indication of the agreement among the final target audience and ultimate end-users of the recommendations. The survey took place in June 2015. Of the 158 EUVAS members surveyed, there were 88 responses (55.7%). There was a large degree of agreement in the voting patterns between EUVAS survey participants and task force members. Notable exceptions were lower grades for the recommendation of the use of rituximab for remission induction in patients with eosinophilic granulomatosis with polyangiitis and for methotrexate and mycophenolate mofetil as remission maintenance agents in patients with granulomatosis with polyangiitis/microscopic polyangiitis by EUVAS members. These results are encouraging and suggest that the voting patterns of the task force are representative of the wider vasculitis community. We recommend future recommendations adopt this approach for data/expert-based treatment guidelines, especially for multisystem diseases

Validation of the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis by disease content experts

The European League Against Rheumatism (EULAR) recommendations for the management of small-vessel and medium-vessel vasculitides were recently updated, with a focus on antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis, and were coendorsed by the European Renal Association-European Dialysis and Transplant Association and European Vasculitis Society (EUVAS).1 The process for formation of such recommendations follows a standard methodology.2 3 Since ANCA-associated vasculitis can present to physicians from a wide range of specialities, a task force was convened with representation from different subspecialisations. Standard practice for voting on the recommendations was followed but, for the first time, they were also voted on by members of a learnt society, which in this case was the EUVAS. EUVAS allows members to join the Society from around the world and as such is an open collaboration of physicians which aims to promote research and education in vasculitis. Results from the Canadian Vasculitis Network revealed significant variations in practice highlighting the need for evidence-based management recommendations for ANCA-associated vasculitis.4 In addition, the publication of large collaborative trials, involving patients with ANCA-associated vasculitis, has advanced the evidence from which conclusions on treatment can be drawn. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis