The tax-inducible actin-bundling protein fascin is crucial for release and cell-to-cell transmission of human T-cell leukemia virus type 1 (HTLV-1)

The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4(+) T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells. Here, we report that Fascin contributes to HTLV-1 transmission. Using single-cycle replication-dependent HTLV-1 reporter vectors, we found that repression of endogenous Fascin by short hairpin RNAs and by Fascin-specific nanobodies impaired gag p19 release and cell-to-cell transmission in 293T cells. In Jurkat T-cells, Tax-induced Fascin expression enhanced virus release and Fascin-dependently augmented cell-to-cell transmission to Raji/CD4(+) B-cells. Repression of Fascin in HTLV-1-infected T-cells diminished virus release and gag p19 transfer to co-cultured T-cells. Spotting the mechanism, flow cytometry and automatic image analysis showed that Tax-induced T-cell conjugate formation occurred Fascin-independently. However, adhesion of HTLV-1-infected MT-2 cells in co-culture with Jurkat T-cells was reduced upon knockdown of Fascin, suggesting that Fascin contributes to dissemination of infected T-cells. Imaging of chronically infected MS9 T-cells in co-culture with Jurkat T-cells revealed that Fascin's localization at tight cell-cell contacts is accompanied by gag polarization suggesting that Fascin directly affects the distribution of gag to budding sites, and therefore, indirectly viral transmission. In detail, we found gag clusters that are interspersed with Fascin clusters, suggesting that Fascin makes room for gag in viral biofilms. Moreover, we observed short, Fascin-containing membrane extensions surrounding gag clusters and clutching uninfected T-cells. Finally, we detected Fascin and gag in long-distance cellular protrusions. Taken together, we show for the first time that HTLV-1 usurps the host cell factor Fascin to foster virus release and cell-to-cell transmission

Recommendations for anesthesia and perioperative management in patients with Ehlers-Danlos syndrome(s)

Ehlers-Danlos syndrome (EDS, ORPHA98249) comprises a group of clinically and genetically heterogeneous heritable connective tissue disorders, chiefly characterized by joint hypermobility and instability, skin texture anomalies, and vascular and soft tissue fragility. As many tissues can be involved, the underlying molecular defect can manifest itself in many organs and with varying degrees of severity, with widespread implications for anesthesia and perioperative management. This review focuses on issues relevant for anesthesia for elective and emergency surgery in EDS. We searched the literature for papers related to all EDS variants; at the moment most of the published data deals with the vascular subtype and, to a lesser extent, classic and hypermobility EDS. Knowledge is fragmented and consists mostly of case reports, small case series and expert opinion. Because EDS patients commonly require surgery, we have summarized some recommendations for general, obstetrical and regional anesthesia, as well as for hemostatic therapy

Eggshells as natural calcium carbonate source in combination with hyaluronan as beneficial additives for bone graft materials, an in vitro study

Introduction: In bone metabolism and the formation especially in bone substitution, calcium as basic module is of high importance. Different studies have shown that the use of eggshells as a bone substitute material is a promising and inexpensive alternative. In this in vitro study, the effects of eggshell granulate and calcium carbonate towards primary bovine osteoblasts were investigated. Hyaluronan (HA) was used as artificial extracellular matrix (ECM) for the used cells to facilitate proliferation and differentiation and to mimic the physiological requirements given by the egg in vivo. Methods: Hyaluronan, eggshells, a combination of hyaluronan and eggshells and CaCO3 were applied to the cells as additive to the used standard medium (modified High Growth Enhancement Medium) in a concentration of 0,1 g/l. The effect of the additives in the culture medium was examined by proliferation tests, immunohistochemical staining (anti-collagen type I, anti-osteopontin, anti-osteonectin and anti-osteocalcin) and kinetic oxygen measurements. Results: Our investigations revealed that all investigated additives show beneficial effect on osteoblast activity. Cell proliferation, differentiation and the metabolic activity of the differentiated cells could be influenced positively. Especially in the case cell cultures treated with eggshells the strongest effects were detected, while for the hyaluronan compared with eggshells, a weaker increase in cell activity was observed. Conclusion: In summary, it can be stated that the investigated components come into consideration as beneficial supplements for bone graft materials especially for maxillo facial surgery application.<br

Circum-Arctic changes in the flow of glaciers and ice caps from satellite SAR data between the 1990s and 2017

We computed circum-Arctic surface velocitymaps of glaciers and ice caps over the Canadian Arctic, Svalbard and the Russian Arctic for at least two times between the 1990s and 2017 using satellite SAR data. Our analyses are mainly performed with offset-tracking of ALOS-1 PALSAR-1 (2007–2011) and Sentinel-1 (2015–2017) data. In certain cases JERS-1 SAR (1994–1998), TerraSAR-X (2008–2012), Radarsat-2 (2009–2016) and ALOS-2 PALSAR-2 (2015–2016) data were used to fill-in spatial or temporal gaps. Validation of the latest Sentinel-1 results was accomplished by means of SAR data at higher spatial resolution (Radarsat-2Wide Ultra Fine) and ground-basedmeasurements. In general, we observe a deceleration of flow velocities for the major tidewater glaciers in the Canadian Arctic and an increase in frontal velocity along with a retreat of frontal positions over Svalbard and the Russian Arctic. However, all regions have strong accelerations for selected glaciers. The latter developments can be well traced based on the very high temporal sampling of Sentinel-1 acquisitions since 2015, revealing new insights in glacier dynamics. For example, surges on Spitsbergen (e.g., Negribreen, Nathorsbreen, Penckbreen and Strongbreen) have a different characteristic and timing than those over Eastern Austfonna and Edgeoya (e.g., Basin 3, Basin 2 and Stonebreen). Events similar to those ongoing on Eastern Austofonna were also observed over the Vavilov Ice Cap on Severnaya Zemlya and possibly Simony Glacier on Franz-Josef Land. Collectively, there seems to be a recently increasing number of glaciers with frontal destabilization over Eastern Svalbard and the Russian Arctic compared to the 1990s

Cerebral differences in explicit and implicit emotional processing - An fMRI study

The processing of emotional facial expression is a major part of social communication and understanding. In addition to explicit processing, facial expressions are also processed rapidly and automatically in the absence of explicit awareness. We investigated 12 healthy subjects by presenting them with an implicit and explicit emotional paradigm. The subjects reacted significantly faster in implicit than in explicit trials but did not differ in their error ratio. For the implicit condition increased signals were observed in particular in the thalami, the hippocampi, the frontal inferior gyri and the right middle temporal region. The analysis of the explicit condition showed increased blood-oxygen-level-dependent signals especially in the caudate nucleus, the cingulum and the right prefrontal cortex. The direct comparison of these 2 different processes revealed increased activity for explicit trials in the inferior, superior and middle frontal gyri, the middle cingulum and left parietal regions. Additional signal increases were detected in occipital regions, the cerebellum, and the right angular and lingual gyrus. Our data partially confirm the hypothesis of different neural substrates for the processing of implicit and explicit emotional stimuli. Copyright (c) 2007 S. Karger AG, Basel

Using simulated fluorescence cell micrographs for the evaluation of cell image segmentation algorithms

The zip archive contains real images showing macrophages. (ZIP 28979 kb

On which common ground to build? Transferable knowledge across cases in transdisciplinary sustainability research

To support societal problem solving, transdisciplinary research (TDR) uses knowledge co-production focusing on relevance and validity in a studied case and its particular social–ecological context. In the first instance, the resulting situated knowledge seems to be restricted to these single cases. However, if some of the knowledge generated in TDR could be used in other research projects, this would imply that there is a body of knowledge representing this special type of research. This study used a qualitative approach based on the methodology of grounded theory to empirically examine what knowledge is considered transferable to other cases, if any. 30 leaders of 12 Swiss-based TDR projects in the field of sustainable development were interviewed, representing both academia and practice. The transferable knowledge we found consists of the following: (1) Transdisciplinary principles, (2) transdisciplinary approaches, (3) systematic procedures, (4) product formats, (5) experiential know-how, (6) framings and (7) insights, data and information. The discussion of TDR has predominantly been focusing on transdisciplinary principles and approaches. In order to take knowledge co-production in TDR beyond an unmanageable field of case studies, more efforts in developing and critically discussing transferable knowledge of the other classes are needed, foremost systematic procedures, product formats and framings

Histologische Veränderungen an peripheren Nerven nach peri- und intraneuraler Injektion von Bupivacain versus Bupivacain & Clonidin in einem experimentellen Regionalanästhesiemodell

Einleitung: Sowohl intra- als auch perineurale Injektionen von Lokalanästhetika führen zu Inflammationsreaktionen im jeweiligen Nerven und sind daher einer der Hauptgründe für postinterventionelle neurologische Dysfunktionen. Während einer Regionalanästhesie werden regelmäßig Adjuvanzien eingesetzt, um die erforderliche Dosis an Lokalanästhetika zu reduzieren und deren Wirkdauer zu verlängern. Die Auswirkungen der eingesetzten Adjuvanzien auf diese Entzündungsreaktion sind bisher nicht ausreichend untersucht worden. Das Ziel der vorliegenden Arbeit war es, den Effekt von Clonidin auf die durch Bupivacain hervorgerufene Inflammationsreaktion zu untersuchen. Material und Methoden: Mit Hilfe von insgesamt 13 vollanästhesierten Hausschweinen wurden 111 Nerven mit den Testlösungen aufbereitet. Die Nerven wurden 48 Stunden vor der Entnahme entweder mit NaCl, Bupivacain, oder Bupivacain & Clonidin perineural oder intraneural bearbeitet. Nach der Entnahme wurden die Nerven histologisch aufbereitet (HE-Färbung, CD68-Färbung und Klüver-Barrera-Färbung). Durch die folgende verblindete mikroskopische Analyse wurden den Nerven abhängig vom Grad ihrer traumabedingten Schädigung Score-Werte von 0 (keine Schädigung) bis 4 (starke Schädigung) zugeteilt. Ergebnisse: Beim Vergleich der intraneuralen Injektion von Bupivacain mit der intraneuralen Injektion von Bupivacain & Clonidin konnte kein signifikanter Unterschied in der Nerventraumatisierung festgestellt werden (p=0,372). Ebenso zeigte sich kein signifikanter Unterschied beim Vergleich der Injektionskompartimente (perineural vs. intraneural) miteinander. In der Interventionsgruppe „Bupivacain intraneural“ zeigte sich jedoch stets ein signifikant höherer Nervenschaden als in den negativen Kontrollgruppen (0,007 bzw. 0,008). Schlussfolgerung: In der vorliegenden Studie konnte kein antiinflammatorischer Effekt von Clonidin auf die durch Bupivacain ausgelöste Entzündungsreaktion nach intraneuraler Injektion nachgewiesen werden. Ebenso zeigte sich kein Unterschied bzgl. der Lokalisation der Injektion. Intraneurale Injektionen führten nicht zu stärkeren histologischen Schäden

Simulated movies of fluorescently stained bacteria

Wiesmann V, Bergler M, Münzenmayer C, Wittenberg T. Simulated movies of fluorescently stained bacteria. Fraunhofer Institute for Integrated Circuits, Erlangen, Germany; 2017.Simulated biomovies of fluorescent cells were created by employing cell simulation based on shape, texture, growth and motion information. They are depicted in fluorescent channels where noise and other artifacts were additionally modeled. While the original cell simulation software (Wiesmann et al. 2013) has been extended for biomovie simulation, the step for bacterial growth simulation is similar to image simulation. First, the cell shape is calculated. Second, the cell position on the image grid is calculated. Third, the cell texture is added. Fourth and last, imaging artifacts and noise are added to the final image