Besnoitia besnoiti infection alters both endogenous cholesterol de novo synthesis and exogenous LDL uptake in host endothelial cells

Besnoitia besnoiti, an apicomplexan parasite of cattle being considered as emergent in Europe, replicates fast in host endothelial cells during acute infection and is in considerable need for energy, lipids and other building blocks for offspring formation. Apicomplexa are generally considered as defective in cholesterol synthesis and have to scavenge cholesterol from their host cells for successful replication. Therefore, we here analysed the influence of B. besnoiti on host cellular endogenous cholesterol synthesis and on sterol uptake from exogenous sources. GC-MS-based profiling of cholesterol-related sterols revealed enhanced cholesterol synthesis rates in B. besnoiti-infected cells. Accordingly, lovastatin and zaragozic acid treatments diminished tachyzoite production. Moreover, increased lipid droplet contents and enhanced cholesterol esterification was detected and inhibition of the latter significantly blocked parasite proliferation. Furthermore, artificial increase of host cellular lipid droplet disposability boosted parasite proliferation. Interestingly, lectin-like oxidized low density lipoprotein receptor 1 expression was upregulated in infected endothelial hostcells, whilst low density lipoproteins (LDL) receptor was not affected by parasite infection. However, exogenous supplementations with non-modified and acetylated LDL both boosted B. besnoiti proliferation. Overall, current data show that B. besnoiti simultaneously exploits both, endogenous cholesterol biosynthesis and cholesterol uptake from exogenous sources, during asexual replication

Characterization of homogeneous tissue phantoms for performance tests in diffuse optics

Solid homogeneous turbid phantoms can be employed to mimic the attenuation and angular distribution of light emerging from tissue, e.g., to assess the responsivity of the detection system of diffuse optics instrumentation and to support standardized performance tests of functional near-infrared spectroscopy devices. We present three methods to quantify the wavelength-dependent diffuse transmittance, relying on (1) measurement of radiance exiting the phantom by a detector far from the exit aperture, (2) simple recording of radiance by a power meter close to the exit aperture and correction for the finite distance between phantom surface and detector, (3) determination of the reduced scattering and absorption coefficients by time-resolved diffuse transmittance measurements and forward calculation of the time-integrated diffuse transmittance based on the diffusion model. The implications of the different approximations related to these approaches are discussed. The various methods were applied to characterize solid slab phantoms, and the results were compared. Specifically, for an epoxy-resin based phantom having a thickness of 2 cm, a reduced scattering coefficient of about 0.5/mm and an absorption coefficient of about 0.01/mm, the diffuse transmittance values obtained by the three different methods were found to agree within about 10%

Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients

<p>Abstract</p> <p>Background</p> <p>Survivin, a member of the inhibitor of apoptosis-protein family suppresses apoptosis and regulates cell division. It is strongly overexpressed in the vast majority of cancers. We were interested if survivin detected by immunohistochemistry has prognostic relevance especially for patients of the two soft tissue sarcoma entities leiomyosarcoma and synovial sarcoma.</p> <p>Methods</p> <p>Tumors of leiomyosarcoma (n = 24) and synovial sarcoma patients (n = 26) were investigated for their expression of survivin by immunohistochemistry. Survivin expression was assessed in the cytoplasm and the nucleus of tumor cells using an immunoreactive scoring system (IRS).</p> <p>Results</p> <p>We detected a survivin expression (IRS > 2) in the cytoplasm of 20 leiomyosarcomas and 22 synovial sarcomas and in the nucleus of 12 leiomyosarcomas and 9 synovial sarcomas, respectively. There was no significant difference between leiomyosarcoma and synovial sarcoma samples in their cytoplasmic or nuclear expression of survivin. Next, all sarcoma patients were separated in four groups according to their survivin expression in the cytoplasm and in the nucleus: group 1: negative (IRS 0 to 2); group 2: weak (IRS 3 to 4); group 3: moderate (IRS 6 to 8); group 4: strong (IRS 9 to 12). In a multivariate Cox's regression hazard analysis survivin expression detected in the cytoplasm or in the nucleus was significantly associated with overall survival of patients in group 3 (RR = 5.7; P = 0.004 and RR = 5.7; P = 0.022, respectively) compared to group 2 (reference). Patients whose tumors showed both a moderate/strong expression of survivin in the cytoplasm and a moderate expression of survivin in the nucleus (in both compartments IRS ≥ 6) possessed a 24.8-fold increased risk of tumor-related death (P = 0.003) compared to patients with a weak expression of survivin both in the cytoplasm and in the nucleus.</p> <p>Conclusion</p> <p>Survivin protein expression in the cytoplasma and in the nucleus detected by immunohistochemistry is significantly associated with prognosis of leiomyosarcoma and synovial sarcoma patients.</p

Characterizing the cross dispersion reflection gratings of CRIRES+

The CRIRES+ project attempts to upgrade the CRIRES instrument into a cross dispersed Echelle spectrograph with a simultaneous recording of 8-10 diffraction orders. In order to transform the CRIRES spectrograph into a cross-dispersing instrument, a set of six reflection gratings, each one optimized for one of the wavelength bands CRIRES+ will operate in (YJHKLM), will be used as cross dispersion elements in CRIRES+. Due to the upgrade nature of the project, the choice of gratings depends on the fixed geometry of the instrument. Thus, custom made gratings would be required to achieve the ambitious design goals. Custom made gratings have the disadvantage, though, that they come at an extraordinary price and with lead times of more than 12 months. To mitigate this, a set of off-the-shelf gratings was obtained which had grating parameters very close to the ones being identified as optimal. To ensure that the rigorous specifications for CRIRES+ will be fulfilled, the CRIRES+ team started a collaboration with the Physikalisch-Technische Bundesanstalt Berlin (PTB) to characterize gratings underconditions similar to the operating conditions in CRIRES+ (angle of incidence, wavelength range). The respective test setup was designed in collaboration between PTB and the CRIRES+ consortium. The PTB provided optical radiation sources and calibrated detectors for each wavelength range. With this setup, it is possible to measure the absolute efficiency of the gratings both wavelength dependent and polarization state dependent in a wavelength range from 0.9 μm to 6 μm

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Determination of energy scales in few-electron double quantum dots

The capacitive couplings between gate-defined quantum dots and their gates vary considerably as a function of applied gate voltages. The conversion between gate voltages and the relevant energy scales is usually performed in a regime of rather symmetric dot-lead tunnel couplings strong enough to allow direct transport measurements. Unfortunately, this standard procedure fails for weak and possibly asymmetric tunnel couplings, often the case in realistic devices. We have developed methods to determine the gate voltage to energy conversion accurately in the different regimes of dot-lead tunnel couplings and demonstrate strong variations of the conversion factors. Our concepts can easily be extended to triple quantum dots or even larger arrays

Radiometric Measurement of Thermodynamic Temperatures and Comparison with the International Temperature Scale (ITS-90) in the Range from 419 °C to 660 °C

Die zur Zeit gültige Internationale Temperaturskala von 1990 (ITS-90) als eine Approximation der thermodynamischen Temperaturskala stützt sich im Hochtemperaturbereich auf einem Referenzwert bei 730 K. Die thermodynamische Temperatur dieses Referenzwertes wurde am National Institute of Technology, USA (NIST) mit einem Gasthermometer konstanten Volumens in zwei Experimenten 1976 und, mit einer geringfügig modifizierten Apparatur, 1989 bestimmt. Zwischen diesen beiden Messungen besteht ein großer signifikanter Unterschied von 30 mK, da als erweiterte Messunsicherheit (Erweiterungsfaktor k=3, der Wert der Messgröße liegt mit einer Wahrscheinlichkeit von 99 % in diesem Intervall) für die Messergebnisse jeweils 6 mK (1976) und 9 mK (1989) angegeben wurde. Das NIST konnte das Problem dieser systematischen Abweichung nicht lösen. Für die Konstruktion der ITS-90 wurde, da keine andere unabhängige primärthermometrische Methode zur Verfügung stand, deshalb der Mittelwert der beiden Messungen für den Referenzwert gewählt. Weil die Wahl des Mittelwerts als Referenzwert ohne eine fundierte physikalische Begründung getroffen wurde, ergibt sich die Notwendigkeit, die thermodynamische Temperatur des ITS-90-Referenzwertes bei 730 K unabhängig von der Gasthermometrie zu messen, um so eine Verbesserung der thermodynamischen Basis der ITS-90 und damit einer Verringerung der thermodynamischen Unsicherheit bei der Bestimmung von Temperaturen im Hochtemperaturbereich zu erreichen. Ziel der vorliegenden Arbeit war, mit einer von der Gasthermometrie unabhängigen primärthermometrischen Methode, der spektralradiometrischen Messung thermodynamischer Temperaturen an einem Schwarzen Strahler, das Problem der großen systematischen Abweichung zwischen den beiden gasthermometrisch am NIST bestimmten Werten für die thermodynamische Temperatur des ITS-90-Referenzwertes zu lösen. Zur Beantwortung dieser Fragestellung wurden in der vorliegenden Arbeit an der Physikalisch-Technischen Bundesanstalt (PTB) thermodynamische Temperaturen durch Messung der spektralen Bestrahlungsstärke an einem Hohlraumstrahler mit absolut kalibrierten Filterradiometern als Detektoren im Bereich zwischen dem Zink-Fixpunkt (692 K) und dem Aluminium-Fixpunkt (933 K) bestimmt und die Abweichung zwischen der thermodynamischen und der simultan bestimmten ITS-90-Temperatur des Hohlraumstrahlers gemessen. Die Zielsetzung der vorliegenden Arbeit wurde durch eine konsequente Weiterentwicklung der Präzisionsradiometrie an Schwarzen Strahlern erreicht. Es konnte mit einer relativen Unsicherheit von 0,01 % gezeigt werden, dass der Hohlraumstrahler mit einem Emissionsgrad von 0,9999 für den untersuchten Temperaturbereich eine nahezu ideale Realisierung eines Schwarzen Strahlers darstellt. Durch Rückführung auf ein bei 5 K betriebenes elektrisches Substitutionsradiometer (Kryoradiometer) als Detektor-Primärnormal wurden vier verschiedene Filterradiometer im nahen Infrarot mit relativen Unsicherheiten bis hinab zu 0,03 % bezüglich der spektralen Bestrahlungsstärkeempfindlichkeit kalibriert. Unter diesen Voraussetzungen ist es erstmals gelungen, absolutradiometrisch thermodynamische Temperaturen mit einer Unsicherheit von 15 mK am Referenzwert bei 730 K zu bestimmen. Innerhalb der Standardunsicherheit (k=1) stimmen die Ergebnisse für die thermodynamische Temperatur des Referenzwertes mit dem durch Edsinger und Schooley am NIST 1989 erhaltenen Ergebnis sehr gut überein, die Resultate von Guildner und Edsinger (1976) weichen signifikant ab. Die vorliegende Arbeit stellt dadurch, dass ein neuer, absolutradiometrisch gemessener Wert mit einer wohlbegründeten Unsicherheit für die thermodynamische Temperatur des Referenzwertes bestimmt wurde, einen wesentlichen Beitrag zur Verbesserung der thermodynamischen Basis der ITS-90 im Hochtemperaturbereich dar

Influence of circulating prolactin increased by a psychotropic drug on gonadotrophin and progesterone secretion

The purpose of the present communication is to report on the effects of high levels of circulating prolactin on gonadotropin and progesterone secretion during the luteal phase of the menstrual cycle. Purified human prolactin not being available, endogenous prolactin was increased in six normal cycling women by daily oral administration of 150 mg sulpiride starting at midcycle. Blood samples were collected daily during a control cycle and during the cycle under treatment. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were measured by radioimmunoassay methods. Prolactin results were expressed in terms of a laboratory standard: 1.0 unit (U) is the amount of immunoreactive prolactin contained in 1.0 ml of a pool of sera rich in prolactin. Serum progesterone was measured by competitive protein binding. All control cycles were ovulatory. The length of the luteal phase ranged from 14 to 15 days. In all cycles under treatment, there was a significant rise (p < 0.001) in serum prolactin starting the day of sulpiride administration and sustained during the entire luteal phase: the mean serum prolactin was 790 mU/ml as compared to 120 mU/ml during the luteal phase of the control cycles. Two cases showed no LH surge and no rise in progesterone secretion. In three out of the other four cases, the LH peaks occurred under treatment; they were lower than in the corresponding control cycles. In the four ovulatory cycles, the length of the luteal phase ranged from 11 to 14 days and was shortened by 1 to 4 days. During the luteal phase, the mean levels of serum LH (2.5 mIU/ml), FSH (5.0 mIU/ml) and progesterone (0.009 μg/ml) were significantly lower (p < 0.001) than those of the control cycles (LH = 7.4 mIU/ml; FSH = 10.0 mIU/ml; progesterone = 0.012 μg/ml).SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

The garlic ingredient diallyl sulfide inhibits cytochrome P450 2E1 dependent bioactivation of acrylamide to glycidamide. Toxicol Lett

Abstract Genotoxic effects of acrylamide are supposed to result from oxidative biotransformation to glycidamide. After incubation of rat liver slices with acrylamide we detected free glycidamide using a liquid chromatography tandem mass spectrometric method. Glycidamide formation was diminished in the presence of the cytochrome P450 2E1 inhibitor diallyl sulfide (DAS), which is a specific ingredient of garlic. This may be relevant to human health since the suggested carcinogenic risk of dietary acrylamide may be reduced by concomitant intake of garlic