Plasmodium bergheisporozoites in nonreplicative vacuole are eliminated by a PI3P-mediated autophagy-independent pathway

The protozoan parasitePlasmodium, causative agent of malaria, invades hepatocytes by invaginating the host cell plasma membrane and forming a parasitophorous vacuole membrane (PVM). Surrounded by this PVM, the parasite undergoes extensive replication. Parasites inside a PVM provoke thePlasmodium-associated autophagy-related (PAAR) response. This is characterised by a long-lasting association of the autophagy marker protein LC3 with the PVM, which is not preceded by phosphatidylinositol 3-phosphate (PI3P)-labelling. Prior to productive invasion, sporozoites transmigrate several cells and here we describe that a proportion of traversing sporozoites become trapped in a transient traversal vacuole, provoking a host cell response that clearly differs from the PAAR response. These trapped sporozoites provoke PI3P-labelling of the surrounding vacuolar membrane immediately after cell entry, followed by transient LC3-labelling and elimination of the parasite by lysosomal acidification. Our data suggest that this PI3P response is not only restricted to sporozoites trapped during transmigration but also affects invaded parasites residing in a compromised vacuole. Thus, host cells can employ a pathway distinct from the previously described PAAR response to efficiently recognise and eliminatePlasmodiumparasites.Host-parasite interactio

Emergence of Respiratory Streptococcus agalactiae Isolates in Cystic Fibrosis Patients

Streptococcus agalactiae is a well-known pathogen for neonates and immunocompromized adults. Beyond the neonatal period, S. agalactiae is rarely found in the respiratory tract. During 2002–2008 we noticed S. agalactiae in respiratory secretions of 30/185 (16%) of cystic fibrosis (CF) patients. The median age of these patients was 3–6 years older than the median age CF patients not harboring S. agalactiae. To analyze, if the S. agalactiae isolates from CF patients were clonal, further characterization of the strains was achieved by capsular serotyping, surface protein determination and multilocus sequence typing (MLST). We found a variety of sequence types (ST) among the isolates, which did not substantially differ from the MLST patterns of colonizing strains from Germany. However serotype III, which is often seen in colonizing strains and invasive infections was rare among CF patients. The emergence of S. agalactiae in the respiratory tract of CF patients may represent the adaptation to a novel host environment, supported by the altered surfactant composition in older CF patients

Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study.

Funder: National Institute for Health Research (NIHR)INTRODUCTION: Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV-2 infection on the brain by diverse potentially pathogenic mechanisms, and with high reliability across multiple sites and scanner manufacturers. Here we describe the development of such a protocol, based upon the UK Biobank, and its validation with a travelling heads study. A multi-modal brain MRI protocol comprising sequences for T1-weighted MRI, T2-FLAIR, diffusion MRI (dMRI), resting-state functional MRI (fMRI), susceptibility-weighted imaging (swMRI), and arterial spin labelling (ASL), was defined in close approximation to prior UK Biobank (UKB) and C-MORE protocols for Siemens 3T systems. We iteratively defined a comparable set of sequences for General Electric (GE) 3T systems. To assess multi-site feasibility and between-site variability of this protocol, N = 8 healthy participants were each scanned at 4 UK sites: 3 using Siemens PRISMA scanners (Cambridge, Liverpool, Oxford) and 1 using a GE scanner (King's College London). Over 2,000 Imaging Derived Phenotypes (IDPs), measuring both data quality and regional image properties of interest, were automatically estimated by customised UKB image processing pipelines (S2 File). Components of variance and intra-class correlations (ICCs) were estimated for each IDP by linear mixed effects models and benchmarked by comparison to repeated measurements of the same IDPs from UKB participants. Intra-class correlations for many IDPs indicated good-to-excellent between-site reliability. Considering only data from the Siemens sites, between-site reliability generally matched the high levels of test-retest reliability of the same IDPs estimated in repeated, within-site, within-subject scans from UK Biobank. Inclusion of the GE site resulted in good-to-excellent reliability for many IDPs, although there were significant between-site differences in mean and scaling, and reduced ICCs, for some classes of IDP, especially T1 contrast and some dMRI-derived measures. We also identified high reliability of quantitative susceptibility mapping (QSM) IDPs derived from swMRI images, multi-network ICA-based IDPs from resting-state fMRI, and olfactory bulb structure IDPs from T1, T2-FLAIR and dMRI data. CONCLUSION: These results give confidence that large, multi-site MRI datasets can be collected reliably at different sites across the diverse range of MRI modalities and IDPs that could be mechanistically informative in COVID brain research. We discuss limitations of the study and strategies for further harmonisation of data collected from sites using scanners supplied by different manufacturers. These acquisition and analysis protocols are now in use for MRI assessments of post-COVID patients (N = 700) as part of the ongoing COVID-CNS study

Technical Design Report for the: PANDA Micro Vertex Detector

This document illustrates the technical layout and the expected performance of the Micro Vertex Detector (MVD) of the PANDA experiment. The MVD will detect charged particles as close as possible to the interaction zone. Design criteria and the optimisation process as well as the technical solutions chosen are discussed and the results of this process are subjected to extensive Monte Carlo physics studies. The route towards realisation of the detector is outlined.Comment: 189 pages, 225 figures, 41 table

Untersuchungen zur Energieübertragung von Röntgen- und Gammastrahlen an biologischen Modellstrukturen

Einzelereignis-Spektren wurden von Co$^{60}$ Gammastrahlung und gefilterten 200 KV Röntgenstrahlen für kugel- und zylinderförmige Volumina von subzellularer Größe gemessen (3,0-0,1$\mu$m). Für die Messungen wurde ein neuartiger wandloser Proportionalzähler entwickelt, der auf einfache Weise in einen Wandzählerverwandelt werden kann. Messungen der Gasverstärkung dieses Zählers ergaben neue Werte für die Gasparameter A und B, die eine Abschätzung der Verstärkung von Proportionalzählern bei hohen elektrischen Feldstärken an der Sammelelektrode (1000 bis 4000 [V$\cdot$Torr$^{-1} \cdot$ cm$^{-1}$]) ermöglichen. Ferner zeigte sich, daß der minimal verwendbare effektive Zählerdurchmesser 0,1 $\mu$m beträgt, wenn Messungen mit Strahlungen niedriger LET durchgeführt werden.Die Einzelereignisspektren wurden mit zwei zylindrischen Zählern (wandlos und mit Wand) und einem 2" Rossi-Zähler gemessen und die durch die Strahlenqualität, den Wandeffekt und die Zählergeometrie bedingten Unterschiede untersucht. - Die Energiedeposition mit der höchsten Wahrscheinlichkeit betrug bei der Co$^{60}$ -Strahlung $\sim$ 0,17 KeV/$\mu$m und bei der Röntgenstrahlung $\sim$ 0,65 KeV/$\mu$m. -Im Fall der Co$^{60}$-Bestrahlung sind die Wahrscheinlichkeitsverteilungen nahezu identisch für alle verwendeten Zähler. Dagegen zeigt sich für Röntgenstrahlen sowohl ein Einfluß der Zählergeometrie als auch des Wandeffekts, was auf die erhöhte LET der Röntgenstrahlen gegenüber Co$^{60}$-Gammastrahlen zurückgeführt werden kann. Die Mittelwerte und Varianzen der Verteilungen wurden berechnet und für Volumina von Chromosomengröße (100 $\mathring{A}$) extrapoliert

Plasmodium berghei sporozoites in nonreplicative vacuoles are eliminated by a PI3P-mediated autophagy-independent pathway.

The protozoan parasite Plasmodium, causative agent of malaria, invades hepatocytes by invaginating the host cell plasma membrane and forming a parasitophorous vacuole membrane (PVM). Surrounded by this PVM, the parasite undergoes extensive replication. Parasites inside a PVM provoke the Plasmodium-associated autophagy-related (PAAR) response. This is characterized by a long-lasting association of the autophagy marker protein LC3 with the PVM, which is not preceded by phosphatidylinositol 3-phosphate (PI3P)-labelling. Prior to productive invasion, sporozoites transmigrate several cells and here we describe that a proportion of traversing sporozoites become trapped in a transient traversal vacuole, provoking a host cell response that clearly differs from the PAAR response. These trapped sporozoites provoke PI3P-labelling of the surrounding vacuolar membrane immediately after cell entry, followed by transient LC3-labelling and elimination of the parasite by lysosomal acidification. Our data suggest that this PI3P response is not only restricted to sporozoites trapped during transmigration but also affects invaded parasites residing in a compromised vacuole. Thus, host cells can employ a pathway distinct from the previously described PAAR response to efficiently recognize and eliminate Plasmodium parasites. This article is protected by copyright. All rights reserved