Microstructured blood vessel surrogates reveal structural tropism of motile malaria parasites

Plasmodium sporozoites, the highly motile forms of the malaria parasite, are transmitted naturally by mosquitoes and traverse the skin to find, associate with, and enter blood capillaries. Research aimed at understanding how sporozoites select blood vessels is hampered by the lack of a suitable experimental system. Arrays of uniform cylindrical pillars can be used to study small cells moving in controlled environments. Here, an array system displaying a variety of pillars with different diameters and shapes is developed in order to investigate how Plasmodium sporozoites associate to the pillars as blood vessel surrogates. Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters reveals that the crescent-shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito, malaria parasites may use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream

Luft-Wasser Experimente im vertikalen DN200-Rohr

Die im Rahmen dieser Versuchsserie erzielten umfangreichen experimentellen Ergebnisse bilden eine hochwertige Datenbasis für Luft-Wasser-Strömungen in einem vertikalen DN200-Rohr, die für die Entwicklung und Validierung von CFD-Modellen, beispielweise bzgl. Blasenkoaleszenz und -fragmentierung, genutzt werden können. Besonderes interessant ist die Untersuchung der Entwicklung der Zweiphasenströmung über der Rohrhöhe. Aus diesem Grund wurden für jede der 92 betrachteten Kombinationen aus Gas- und Wasser-Volumenstromdichten bis zu 18 Messungen mit variablen Abständen zwischen Gaseinspeisung und Messebene durchgeführt. Dabei wurde der Druck an der Gaseinspeisestelle konstant auf 0,25 MPa(a) gehalten. Diese Randbedingung bietet den Vorteil, dass die so gemessenen Daten die Entwicklung der Strömung über der Rohrhöhe widerspiegeln, d.h. eine Konfiguration beschreiben, bei der das Gas an einer festen Höhenposition eingespeist wird und die Messungen in verschiedenen darüberliegenden Ebenen erfolgen. Wesentliche Ergebnisse dieser Messserie sind radiale zeitgemittelte Profile für den Gasgehalt und die Gasgeschwindigkeit sowie zeit- und querschnittsgemittelte Blasengrößenverteilungen. Außerdem liegen blasengrößen- und ortsaufgelöste Gasgehaltsdaten vor. Wie bereits bei früheren Versuchsserien wurden auch in diesem Fall die Strömungsformen analysiert, wobei die Klassifizierung anhand der Blasengröße erfolgte. Ein wesentlicher Bestandteil dieser neuen Luft/Wasser-Versuche war die Qualitäts- und Plausibilitätsprüfung der Messdaten. Es konnte festgestellt werden, dass die Daten einen eindeutigen, widerspruchsfreien Trend bzgl. ihrer Entwicklung mit zunehmendem Abstand von der Gaseinspeisung aufweisen. Zur Plausibilitätsprüfung wurden Vergleiche des Gasgehaltsverlaufes über der Rohrhöhe mit theoretisch zu erwartenden Kurven durchgeführt. Zusätzlich zu diesen Ergebnissen enthält der Bericht eine Einschätzung des Einflusses des Bohrungsdurchmessers an der Gaseinspeisung auf die sich einstellende Strömung

Moving in extreme environments:extreme loading; carriage versus distance

This review addresses human capacity for movement in the context of extreme loading and with it the combined effects of metabolic, biomechanical and gravitational stress on the human body. This topic encompasses extreme duration, as occurs in ultra-endurance competitions (e.g. adventure racing and transcontinental races) and expeditions (e.g. polar crossings), to the more gravitationally limited load carriage (e.g. in the military context). Juxtaposed to these circumstances is the extreme metabolic and mechanical unloading associated with space travel, prolonged bedrest and sedentary lifestyle, which may be at least as problematic, and are therefore included as a reference, e.g. when considering exposure, dangers and (mal)adaptations. As per the other reviews in this series, we describe the nature of the stress and the associated consequences; illustrate relevant regulations, including why and how they are set; present the pros and cons for self versus prescribed acute and chronic exposure; describe humans’ (mal)adaptations; and finally suggest future directions for practice and research. In summary, we describe adaptation patterns that are often U or J shaped and that over time minimal or no load carriage decreases the global load carrying capacity and eventually leads to severe adverse effects and manifest disease under minimal absolute but high relative loads. We advocate that further understanding of load carrying capacity and the inherent mechanisms leading to adverse effects may advantageously be studied in this perspective. With improved access to insightful and portable technologies, there are some exciting possibilities to explore these questions in this context

Skyrmion Hall Effect Revealed by Direct Time-Resolved X-Ray Microscopy

Magnetic skyrmions are highly promising candidates for future spintronic applications such as skyrmion racetrack memories and logic devices. They exhibit exotic and complex dynamics governed by topology and are less influenced by defects, such as edge roughness, than conventionally used domain walls. In particular, their finite topological charge leads to a predicted "skyrmion Hall effect", in which current-driven skyrmions acquire a transverse velocity component analogous to charged particles in the conventional Hall effect. Here, we present nanoscale pump-probe imaging that for the first time reveals the real-time dynamics of skyrmions driven by current-induced spin orbit torque (SOT). We find that skyrmions move at a well-defined angle {\Theta}_{SH} that can exceed 30{\deg} with respect to the current flow, but in contrast to theoretical expectations, {\Theta}_{SH} increases linearly with velocity up to at least 100 m/s. We explain our observation based on internal mode excitations in combination with a field-like SOT, showing that one must go beyond the usual rigid skyrmion description to unravel the dynamics.Comment: pdf document arxiv_v1.1. 24 pages (incl. 9 figures and supplementary information

ADAM15 mediates upregulation of Claudin-1 expression in breast cancer cells

A Disintegrin and Metalloproteinase-15 (ADAM15) is a transmembrane protein involved in protein ectodomain shedding, cell adhesion and signalling. We previously cloned and characterised alternatively spliced variants of ADAM15 that differ in their intracellular domains and demonstrated correlation of the expression of specific variants with breast cancer prognosis. In this study we have created isogenic cell panels (MDA-MB-231 and MCF-7) expressing five ADAM15 variants including wildtype and catalytically inactive forms. The expression of ADAM15 isoforms in MDA-MB-231 cells led to cell clustering to varying degree, without changes in EMT markers vimentin, slug and E-cadherin. Analysis of tight junction molecules revealed ADAM15 isoform specific, catalytic function dependent upregulation of Claudin-1. The expression of ADAM15A, and to a lesser degree of C and E isoforms led to an increase in Claudin-1 expression in MDA-MB-231 cells, while ADAM15B had no effect. In MCF-7 cells, ADAM15E was the principal variant inducing Claudin-1 expression. Sh-RNA mediated down-regulation of ADAM15 in ADAM15 over-expressing cells reduced Claudin-1 levels. Additionally, downregulation of endogenous ADAM15 expression in T47D cells by shRNA reduced endogenous Claudin-1 expression confirming a role for ADAM15 in regulating Claudin-1 expression. The PI3K/Akt/mTOR pathway was involved in regulating Claudin-1 expression downstream of ADAM15. Immunofluorescence analysis of MDA-MB-231 ADAM15A expressing cells showed Claudin-1 at cell-cell junctions, in the cytoplasm and nuclei. ADAM15 co-localised with Claudin-1 and ZO1 at cell-cell junctions. Immunoprecipitation analysis demonstrated complex formation between ADAM15 and ZO1/ZO2. These findings highlight the importance of ADAM15 Intra Cellular Domain-mediated interactions in regulating substrate selection and breast cancer cell phenotype

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease