Building a stem cell-based primate uterus.

Funder: Wellcome TrustThe uterus is the organ for embryo implantation and fetal development. Most current models of the uterus are centred around capturing its function during later stages of pregnancy to increase the survival in pre-term births. However, in vitro models focusing on the uterine tissue itself would allow modelling of pathologies including endometriosis and uterine cancers, and open new avenues to investigate embryo implantation and human development. Motivated by these key questions, we discuss how stem cell-based uteri may be engineered from constituent cell parts, either as advanced self-organising cultures, or by controlled assembly through microfluidic and print-based technologies

Pom1 gradient buffering through intermolecular auto-phosphorylation.

Concentration gradients provide spatial information for tissue patterning and cell organization, and their robustness under natural fluctuations is an evolutionary advantage. In rod-shaped Schizosaccharomyces pombe cells, the DYRK-family kinase Pom1 gradients control cell division timing and placement. Upon dephosphorylation by a Tea4-phosphatase complex, Pom1 associates with the plasma membrane at cell poles, where it diffuses and detaches upon auto-phosphorylation. Here, we demonstrate that Pom1 auto-phosphorylates intermolecularly, both in vitro and in vivo, which confers robustness to the gradient. Quantitative imaging reveals this robustness through two system's properties: The Pom1 gradient amplitude is inversely correlated with its decay length and is buffered against fluctuations in Tea4 levels. A theoretical model of Pom1 gradient formation through intermolecular auto-phosphorylation predicts both properties qualitatively and quantitatively. This provides a telling example where gradient robustness through super-linear decay, a principle hypothesized a decade ago, is achieved through autocatalysis. Concentration-dependent autocatalysis may be a widely used simple feedback to buffer biological activities

Dilemmas of Sustainability: On Relevance and Critical Reflection in Sustainability Research; A Guide

The concept of sustainability is increasingly losing its contours. This study reflects on the understanding of sustainability used in research and science. Its authors thus enable us to concisely determine not only concrete contributions to sustainability, but also its limits. Based on an analytical understanding of sustainability and the basic structure of practical dilemmas, the book identifies typical conflicts as causes of dilemmas. Meta-criteria of sustainability allow us to identify dilemmas and to clarify and deal with them practically at an early stage. Finally, the study applies these meta-criteria in concrete project contexts by means of guiding questions for reflection.Der Begriff der Nachhaltigkeit verliert zunehmend an Kontur. Vor diesem Hintergrund gibt dieser Leitfaden die Möglichkeit, das jeweils verwendete Verständnis von Nachhaltigkeit in Forschung und Wissenschaft zu reflektieren und damit den konkreten Beitrag zu Nachhaltigkeit, aber auch die verbundenen Grenzen konkret festzustellen. Ausgehend von einem analytischen Nachhaltigkeitsverständnis und der Klärung der Grundstruktur praktischer Dilemmata benennt der Leitfaden typische Konflikte als Ursache von Dilemmata. Meta-Kriterien der Nachhaltigkeit erlauben, Dilemmata-Früherkennung, -Aufklärung und -Bearbeitung zu unterstützen. Diese werden abschließend mittels Reflexionsleitfaden für die Anwendung in konkreten Projektkontexten operationalisiert

Optical coherence tomography-guided versus angiography-guided implantation of everolimus-eluting bioresorbable vascular scaffolds: Comparison of coverage, apposition and clinical outcome. The ALSTER-OCT ABSORB registry

Background: Suboptimal implantation of everolimus-eluting bioresorbable vascular scaffolds (EE-BVS) leading to strut malapposition and lack of neointima coverage has been hypothesized to be linked to late BVS-thrombosis. Optical coherence tomography (OCT) allows assessing subtle differences in BVS-healing. We aimed to link 6-months OCT-data on EE-BVS coverage and malapposition to implantation technique and clinical outcome. Methods: Twenty-nine consecutive EE-BVS-patients were included. EE-BVS-implantation was guided by angiography in the first 17 patients (group 1). Vessel sizing prior to implantation and implantation result was assessed by OCT in the 12 following patients (group 2). EE-BVS-implantation was performed in both groups with adequate lesion preparation, sizing and systematic high-pressure post-dilatation. All patients received 6-months invasive control including OCT-analysis and clinical follow-up for 2 years. Results: The rate of uncovered struts was group 1: 10.8 ± 10.0%; group 2: 10.6 ± 8.2%, p = 0.934. Target lesion failure due to BVS-thrombosis occurred in 2/17 patients at 9 and 18 months (11.8%, group 1), and no patients in group 2 (p = 0.218). Conclusions: Optical coherence tomography analysis at 6-months following EE-BVS-implantation finds almost 90% of struts to be covered. No difference between OCT vs. angiography-guided EE-BVS-implantation was observed. OCT at 6-months was not able to predict late BVS-thrombosis of EE-BVS

Hepatitis E Virus infection in HIV-infected patients with elevated serum transaminases levels

Increases in aminotransferases levels are frequently encountered in HIV-positive patients and often remain unexplained. The role in this setting and natural history of hepatitis E in HIV-infected patients are unknown. The aim of the study was to assess HEV infection in HIV-infected patients attending a Parisian hospital, with a current or previous cryptogenic hepatitis.191 plasma samples collected from 108 HIV-infected patients with elevated aminotransferases levels were retrospectively tested for the presence of hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index and plasma HEV RNA.One acute infection, documented by positive tests for anti-HEV IgM antibody, low anti-HEV IgG avidity index and plasma HEV RNA (genotype 3e), and three past infections were diagnosed, without any observed case of persistent infection. The acute hepatitis was benign and resolved spontaneously within two weeks. This infection was probably contracted locally. Acute HEV hepatitis can occur in HIV-infected patients but rarely explains cryptogenic hepatitis, at least in an urban HIV population, regardless geographic origin and CD4 counts

Gesellschaftliche Leistungen des Ökolandbaus in den Pilotregionen Nordhessen und Rheinland. regiosöl-Profile.

Der Ökolandbau leistet einen wichtigen Beitrag zu vielen ökologischen und sozialen gesellschaftlichen Zielen. Um diese sozialen und ökologischen Leistungen (söL) durch verschiedene politische und markt-basierte Instrumente besser als bisher honorieren zu können, werden Möglichkeiten zu ihrer Erfassung und Kommunikation entwickelt. Diesem Ansatz liegt das Verständnis zugrunde, dass die Inwertsetzung von sozialen und ökologischen Leistungen in der Landwirtschaft nur über die Kaskade Bewusstsein – Wertschätzung – Wertschöpfung erfolgen kann. Ziel des regiosöl-Vorhabens ist es, die Leistungen des Ökolandbaus durch eine transparente Erfassung in einem regionalen Bezugsraum sichtbarer zu machen. Das Projekt verfolgt 3 spezifische Ziele: (1) eine verbesserte Erfassungsmethode für die söL des Ökolandbaus, (2) die Darstellung der Leistungen in regionalen Profilen, und (3) ein allgemeinverständlicher Kommunikationsansatz. Bestehende Erfassungs-, Kommunikations- und Honorierungsansätze für die gesellschaftlichen Leistungen des Ökolandbaus wurden gesichtet und bestehende Lücken identifiziert. Aufbauend auf der als besonders Praxis-geeigneten Regionalwert-Nachhaltigkeitsanalyse (RWNA) wurden Kriterien und Indikatoren für eine betriebliche und regionale Erfassung der gesellschaftlichen Leistungen des Ökolandbaus entwickelt. Diese regiosöl-Indikatoren wurden gemeinsam mit der RWNA mit Ökobetrieben in den Pilotregionen getestet und bzgl. ihrer Eignung, Aussagekraft und Bewertungsmöglichkeiten eingeschätzt. Für die beiden Pilotregionen wurden in transdisziplinärer Zusammenarbeit mit Praxisakteuren regiosöl-Profile erstellt. Während eine Erfassung von söL auf betrieblicher Ebene die Optimierung der söL-Bereitstellung des Betriebes bezweckt, sollen die Erkenntnisse der auf regionaler Ebene erfassten söL für eine Optimierung der Bereitstellung gesellschaftlicher Leistungen auf regionaler Ebene genutzt werden. Der regiosöl-Profil-Bericht für die Pilotregionen beinhaltet folglich nicht nur eine Status-Quo-Analyse gesellschaftlicher Leistungen des Ökolandbaus in der Region, sondern stellt basierend auf diesen Erkenntnissen auch regionale Handlungsstrategien für die Weiterentwicklung bzw. Verbesserung dieser gesellschaftlichen Leistungen dar und zeigt eine Entwicklungsperspektive auf

Origin and segregation of the human germline

Acknowledgements This work was supported by the Wellcome Investigator Awards in Science (2094)75/Z/17/Z (to MA Surani), the Wellcome Investigator Awards in Science 096738/Z/11/Z (to MA Surani), the BBSRC research grant G103986 (to MA Surani), the Croucher Postdoctoral Research Fellowship (to WWC Tang), the Wellcome 4-Yr PhD Programme in Stem Cell Biology & Medicine (2038)31/Z/16/Z (to A Castillo-Venzor) and the Cambridge Commonwealth European and International Trust (to A Castillo-Venzor), the Isaac Newton Trust (to WWC Tang), the Butterfield Awards of Great Britain Sasakawa Foundation (to T Kobayashi and MA Surani), and the Astellas Foundation for Research on Metabolic Disorders (to T Kobayashi). The marmoset embryo research is generously supported by the Wellcome Trust (WT RG89228, WT RG9242), the Centre for Trophoblast Research, the Isaac Newton Trust, and JSPS KAKENHI 15H02360, 19H05759. TE Boroviak was supported by a Wellcome Sir Henry Dale Fellowship. JC Marioni acknowledges core support from EMBL and from Cancer Research UK (C9545/A29580), which supports MD Morgan. We would like to thank Roger Barker and Xiaoling He for providing human embryonic tissues and Charles Bradshaw for bioinformatics support. We also thank The Weizmann Institute of Science for the WIS2 human PSC line and the Genomics Core Facility of CRUK Cambridge Institute for sequencing services. We thank members of the Surani laboratory for insightful comments and critical reading of the manuscript.Peer reviewedPublisher PD

Dilemmata der Nachhaltigkeit: Zur Relevanz und kritischen Reflexion in der Nachhaltigkeitsforschung; Ein Leitfaden

Der Begriff der Nachhaltigkeit verliert zunehmend an Kontur. Vor diesem Hintergrund gibt dieser Leitfaden die Möglichkeit, das jeweils verwendete Verständnis von Nachhaltigkeit in Forschung und Wissenschaft zu reflektieren und damit den konkreten Beitrag zu Nachhaltigkeit, aber auch die verbundenen Grenzen konkret festzustellen. Ausgehend von einem analytischen Nachhaltigkeitsverständnis und der Klärung der Grundstruktur praktischer Dilemmata benennt der Leitfaden typische Konflikte als Ursache von Dilemmata. Meta-Kriterien der Nachhaltigkeit erlauben, Dilemmata-Früherkennung, -Aufklärung und -Bearbeitung zu unterstützen. Diese werden abschließend mittels Reflexionsleitfaden für die Anwendung in konkreten Projektkontexten operationalisiert.The concept of sustainability is increasingly losing its contours. This study reflects on the understanding of sustainability used in research and science. Its authors thus enable us to concisely determine not only concrete contributions to sustainability, but also its limits. Based on an analytical understanding of sustainability and the basic structure of practical dilemmas, the book identifies typical conflicts as causes of dilemmas. Meta-criteria of sustainability allow us to identify dilemmas and to clarify and deal with them practically at an early stage. Finally, the study applies these meta-criteria in concrete project contexts by means of guiding questions for reflection

The influence of the representation of collagen fibre organisation on the cartilage contact mechanics of the hip joint

The aim of this study was to develop a finite element (FE) hip model with subject-specific geometry and biphasic cartilage properties. Different levels of detail in the representation of fibre reinforcement were considered to evaluate the feasibility to simplify the complex depth-dependent fibre pattern in the native hip joint. A FE model of a cadaveric hip with subject-specific geometry was constructed through micro-computed-tomography (µCT) imaging. The cartilage was assumed to be biphasic and fibre-reinforced with different levels of detail in the fibre representation. Simulations were performed for heel-strike, mid-stance and toe-off during walking and one-leg-stance over 1500s. It was found that the required level of detail in fibre representation depends on the parameter of interest. The contact stress of the native hip joint could be realistically predicted by simplifying the fibre representation to being orthogonally reinforced across the whole thickness. To predict the fluid pressure, depth-dependent fibre organisation is needed but specific split-line pattern on the surface of cartilage is not necessary. Both depth-dependent and specific surface fibre orientations are required to simulate the strains

Altered interaction of physiological activity and behavior affects risky decision-making in ADHD

BackgroundAdult attention-deficit/hyperactivity disorder (ADHD) is often associated with risky decision-making behavior. However, current research studies are often limited by the ability to adequately reflect daily behavior in a laboratory setting. Over the lifespan impairments in cognitive functions appear to improve, whereas affective functions become more severe. We assume that risk behavior in ADHD arises predominantly from deficits in affective processes. This study will therefore aim to investigate whether a dysfunction in affective pathways causes an abnormal risky decision-making (DM) behavior in adult ADHD.MethodsTwenty-eight participants with ADHD and twenty-eight healthy controls completed a battery of questionnaires regarding clinical symptoms, self-assessment of behavior and emotional competence. Furthermore, skin conductance responses were measured during the performance in a modified version of the Balloon Analogue Risk Task. A linear mixed-effects model analysis was used to analyze emotional arousal prior to a decision and after feedback display.ResultsResults showed higher emotional arousal in ADHD participants before decision-making (β = −0.12, SE = 0.05, t = −2.63, p < 0.001) and after feedback display (β = −0.14, SE = 0.05, t = −2.66, p = 0.008). Although risky behavior was greater in HC than in ADHD, we found a significant interaction effect of group and anticipatory skin conductance responses regarding the response behavior (β = 107.17, SE = 41.91, t = 2.56, p = 0.011). Post hoc analyses revealed a positive correlation between anticipatory skin conductance responses and reaction time in HC, whereas this correlation was negative in ADHD. Self-assessment results were in line with the objective measurements.ConclusionWe found altered changes in physiological activity during a risky decision-making task. The results confirm the assumption of an aberrant relationship between bodily response and risky behavior in adult ADHD. However, further research is needed with respect to age and gender when considering physiological activities