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Introduction: Amniotic fluid harbors cells indicative of all three germ layers, and pluripotent fetal amniotic fluid stem cells (AFSs) are considered potentially valuable for applications in cellular therapy and tissue engineering. We investigated whether it is possible to direct the cell fate of AFSs in vivo by transplantation experiments into a particular microenvironment, the mammary fat pad. This microenvironment provides the prerequisites to study stem cell function and the communication between mesenchymal and epithelial cells. On clearance of the endogenous epithelium, the ductal tree can be reconstituted by the transfer of exogenously provided mammary stem cells. Analogously, exogenously provided stem cells from other tissues can be investigated for their potential to contribute to mammary gland regeneration. Methods: We derived pluripotent murine AFSs, measured the expression of stem cell markers, and confirmed their in vitro differentiation potential. AFSs were transplanted into cleared and non cleared fat pads of immunocompromised mice to evaluate their ability to assume particular cell fates under the instructive conditions of the fat-pad microenvironment and the hormonal stimulation during pregnancy. Results: Transplantation of AFSs into cleared fat pads alone or in the presence of exogenous mammary epithelial cells caused their differentiation into stroma and adipocytes and replaced endogenous mesenchymal components surrounding the ducts in co-transplantation experiments. Similarly, transplantation of AFSs into fat pads that had not been previously cleared led to AFS-derived stromal cells surrounding the elongating endogenous ducts. AFSs expressed the marker protein α-SMA, but did not integrate into the myoepithelial cell layer of the ducts in virgin mice. With pregnancy, a small number of AFS-derived cells were present in acinar structures. Conclusions: Our data demonstrate that the microenvironmental cues of the mammary fat pad cause AFSs to participate in mammary gland regeneration by providing mesenchymal components to emerging glandular structures, but do not incorporate or differentiate into ductal epithelial cells.
Schlangengifte enthalten einen ganzen Arzneischrank voller hochwirksamer Stoffe, die binnen kurzer Zeit zu Schock, Lähmung oder unstillbaren Blutungen führen können. Forscher interessieren sich vor allem für Verbindungen, welche die Blutgerinnung hemmen, denn sie könnten pharmakologisch interessante Leitstrukturen für neue Wirkstoffe sein, die das Risiko eines Herzinfarkts, Gehirnschlags und anderer Thrombosen mindern.
Das Phänomen Terrorismus ist regelmäßig Gegenstand aktueller Berichterstattung in den Nachrichten und tritt hierbei deutlich als von Medien abhängige aggressive Taktik in Erscheinung. Seit den Anschlägen auf das New Yorker World Trade Center am 11. September 2001 hat es in verstärkter Form eine zentrale Rolle im öffentlichen Diskurs inne. Darüber hinaus stellt der Themenkomplex ein wiederkehrendes Motiv in den Unterhaltungsmedien dar. Diese nehmen Bezug auf zeitgeschichtliche Kontexte, welche oft in fiktionalisierter Form Ver- oder wenigstens Bearbeitung finden.
Background: Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tissue damage after hemorrhagic shock/resuscitation. Methods: In a prospective controlled double-armed animal trial 24 Munich Mini Pigs (30.3 +/- 3.3 kg) were rapidly haemorrhaged to reach a mean arterial pressure (MAP) of 35 +/- 5 mmHg, maintained hypotensive for 45 minutes, and then were resuscitated with Ringer's solution to baseline MAP. With beginning of resuscitation 12 pigs underwent extracorporeal immune therapy for 3 hours (LIM group) and 12 pigs were resuscitated according to standard medical care (SMC). Haemodynamics, haematologic, metabolic, and organ specific damage parameters were monitored. Neutrophil infiltration was analyzed histologically after 48 and 72 hours. Lipid peroxidation, and apoptosis were specifically determined in lung, bowel, and liver. Results: In the LIM group, neutrophil counts were reduced versus SMC during extracorporeal immune therapy. After 72 hours, the haemodynamic parameters MAP and cardiac output (CO) were significantly better in the LIM group. Histological analyses showed reduction of shock-related neutrophil tissue infiltration in the LIM group, especially in the lungs. Lower amounts of apoptotic cells and lipid peroxidation were found in organs after LIM treatment. Conclusions: Transient Fas-directed extracorporeal immune therapy may protect from posthemorrhagic neutrophil tissue infiltration and tissue damage.
Poster presentation at 5th German Conference on Cheminformatics: 23. CIC-Workshop Goslar, Germany. 8-10 November 2009 Protein kinases are important targets for drug development. The almost identical protein folding of kinases and the common co-substrate ATP leads to the problem of inhibitor selectivity. Type II inhibitors, targeting the inactive conformation of kinases, occupy a hydrophobic pocket with less conserved surrounding amino acids. Human polo-like kinase 1 (Plk1) represents a promising target for approaches to identify new therapeutic agents. Plk1 belongs to a family of highly conserved serine/threonine kinases, and is a key player in mitosis, where it modulates the spindle checkpoint at metaphase/anaphase transition. Plk1 is over-expressed in all today analyzed human tumors of different origin and serves as a negative prognostic marker in cancer patients. The newly identified inhibitor, SBE13, a vanillin derivative, targets Plk1 in its inactive conformation. This leads to selectivity within the Plk family and towards Aurora A. This selectivity can be explained by docking studies of SBE13 into the binding pocket of homology models of Plk1, Plk2 and Plk3 in their inactive conformation. SBE13 showed anti-proliferative effects in cancer cell lines of different origins with EC50 values between 5 microM and 39 microM and induced apoptosis. Increasing concentrations of SBE13 result in increasing amounts of cells in G2/M phase 13 hours after double thymidin block of HeLa cells. The kinase activity of Plk1 was inhibited with an IC50 of 200 pM. Taken together, we could show that carefully designed structure-based virtual screening is well-suited to identify selective type II kinase inhibitors targeting Plk1 as potential anti-cancer therapeutics.
The basic physics of nonrelativistic and electromagnetic ion stopping in hot and ionized plasma targets is thoroughly updated. Corresponding projectile-target interactions involve enhanced projectile ionization and coupling with target free electrons leading to significantly larger energy losses in hot targets when contrasted to their cold homologues. Standard stoppping formalism is framed around the most economical extrapolation of high velocity stopping in cold matter. Further elaborations pay attention to target electron coupling and nonlinearities due to enhanced projectile charge state, as well. Scaling rules are then used to optimize the enhanced stopping of MeV/amu ions in plasmas with electron linear densities nel ~ 10 18 -10 20 cm -2 . The synchronous firing of dense and strongly ionized plasmas with the time structure of bunched and energetic multicharged ion beam then allow to probe, for the first time, the long searched enhanced plasma stopping and projectile charge at target exit. Laser ablated plasmas (SPQR1) and dense linear plasma columns (SPQR2) show up as targets of choice in providing accurate and on line measurements of plasma parameters. Corresponding stopping results are of a central significance in asserting the validity of intense ion beam scenarios for driving thermonuclear pellets. Other applications of note feature thorium induced fission, novel ion sources and specific material processing through low energy ion beams. Last but not least, the given ion beam-plasma target interaction physics is likely to pave a way to the production and diagnostics of warm dense matter (WDM).
Es werden 66 Neu- oder Wiederfunde sowie nicht publizierte Funde von Flechten und flechtenbewohnenden Pilzen in Hessen gemeldet und kurz kommentiert. Sechs Arten sind zugleich Neufunde für Deutschland: Absconditella pauxilla, Acremonium antarcticum, Calicium adaequatum, Psammina inflata, Ramonia chrysophaea und Tubeufia heterodermiae. Die hessische Artenliste umfasst mittlerweile annähernd 1200 Flechten und flechtenbewohnende oder flechtenähnliche Pilze.
Wer sich auf die Suche nach "starken Frauen" des Mittelalters begibt, wird sogleich auf die berühmteste von allen treffen, auf Eleonore, die schöne und selbstbewusste Erbtochter Herzog Wilhelms X. von Aquitanien, Gemahlin erst Ludwigs VII. von Frankreich, danach Heinrichs II. von England. Er wird ihre Gestalt freilich nur undeutlich wahrnehmen, verhüllt von einem dichten Schleier aus Legenden und konventionellen Urteilen, die Eleonore bis in die Gegenwart populär gemacht und sich erstaunlicherweise seit dem Mittelalter kaum geändert haben, immer noch persönliche Motive unterstellend, wo nach politischen Intentionen gefragt werden muss. Obwohl die Herzogin von Aquitanien ihren beiden Ehemännern das Fundament für erweiterte Herrschaft gelegt hatte, wurde ihr Anspruch auf Teilhabe mit diffamierenden Gerüchten abgewehrt, die noch immer reichlich Stoff für moderne psychohistorische Spekulationen liefern. Ein solcher Sumpf lässt sich nur mit Spezialkenntnissen trockenlegen, und diese vermittelt der Autor in seinem sympathisch klar geschriebenen Buch, fundiert durch souveräne Kenntnis der Quellen (darunter das Material für die in Cambridge vorbereitete Edition der Urkunden Eleonores) und der Forschung. ...
We present the analysis of the impact of convection on the composition of the tropical tropopause layer region (TTL) in West-Africa during the AMMA-SCOUT campaign. Geophysica M55 aircraft observations of water vapor, ozone, aerosol and CO2 show perturbed values at altitudes ranging from 14 km to 17 km (above the main convective outflow) and satellite data indicates that air detrainment is likely originated from convective cloud east of the flight. Simulations of the BOLAM mesoscale model, nudged with infrared radiance temperatures, are used to estimate the convective impact in the upper troposphere and to assess the fraction of air processed by convection. The analysis shows that BOLAM correctly reproduces the location and the vertical structure of convective outflow. Model-aided analysis indicates that in the outflow of a large convective system, deep convection can largely modify chemical composition and aerosol distribution up to the tropical tropopause. Model analysis also shows that, on average, deep convection occurring in the entire Sahelian transect (up to 2000 km E of the measurement area) has a non negligible role in determining TTL composition.