julilili42/papers huggingface dataset:
Effect of Anandamide in <i>Plasmodium Berghei</i>-infected Mice
2010-01-01

Eryptosis, the suicidal death of erythrocytes, is characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Triggers of eryptosis include anandamide. Enhanced eryptosis of infected human erythrocytes is expected to delay the development of parasitaemia during infection with Plasmodium, the parasite causing malaria. The present experiments aimed to test, whether anandamide influences eryptosis, parasite growth and/or host survival during in vitro or in vivo infection with Plasmodia. Human erythrocytes were infected in vitro with P. falciparum, and mice in vivo with P. berghei. Parasitemia was determined with Syto16. Phosphatidylserine-exposing erythrocytes were identified by analysing annexin V-binding in FACS analysis. In vitro infection of human erythrocytes was followed by a significant increase in annexin V-binding, an effect slightly enhanced by anandamide (> or = 50 microM), which significantly reduced intraerythrocytic DNA/RNA content and in vitro parasitaemia. In vivo administration of anandamide (5 mg/kg b.w. subcutaneously) blunted the parasitaemia (from 36.9% to 24.2% of circulating erythrocytes 21 days after infection) and significantly enhanced the survival of P. berghei-infected mice (from 0% to 67% 26 days after infection). The percentage of phosphatidylserine-exposing erythrocytes was significantly increased in anandamide-treated infected mice compared to non-treated infected mice. In conclusion, anandamide stimulated eryptosis of infected erythrocytes thus counteracting parasitaemia and a lethal course of the disease.
Effect of Amphotericin B on Parasitemia and Survival of <i>Plasmodium Berghei</i>-infected Mice
2010-01-01

Premature death of Plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. Amphotericin B has previously been shown to trigger suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study thus tested whether amphotericin B exerts a direct effect on Plasmodium falciparum and influences eryptosis of infected erythrocytes, parasitemia and host survival in murine malaria. To this end, human erythrocytes were infected in vitro with Plasmodium falciparum and mice were infected with Plasmodium berghei ANKA by in vivo intraperitoneal injection of parasitized murine erythrocytes (1x10(6)). Half of the infected mice received amphotericin B (1.5 mg/kg b.w. i.v.) from the 8(th) day of infection. Amphotericin B (> or = 1 microM) compromised the intracellular development of the parasite in human erythrocytes as evident from in vitro growth and DNA amplification assays. Amphotericin B further augmented the eryptosis of infected human erythrocytes. The administration of amphotericin B to infected mice tended to delay the increase of parasitemia and significantly delayed host death. All nontreated mice died from malaria within 27 days. In contrast, some 50% of amphotericin B-treated mice survived for more than 27 days after infection. In conclusion, amphotericin B augmented the suicidal death of infected erythrocytes and delayed the lethal course of malaria in Plasmodium berghei infected mice.
FTY720-Induced Suicidal Erythrocyte Death
2010-01-01

FTY720 is a potent anti-inflammatory drug known to trigger suicidal death or apoptosis of a variety of nucleated cells. Erythrocytes may similarly undergo suicidal erythrocyte death or eryptosis. Hallmarks of eryptosis include cell membrane scrambling and cell shrinkage, which are triggered by increase in cytosolic Ca(2+) concentration and ceramide. The present study explored whether FTY720 stimulates eryptosis. Cell membrane scrambling was determined from annexin V-binding, cell shrinkage from forward scatter in FACS analysis, cytosolic Ca(2+) concentration from Fluo3 fluorescence, ceramide formation from fluorescence-labeled antibody binding and hemolysis from the hemoglobin concentration in the supernatant. Within 48 hours exposure to FTY720 (10 μM) significantly increased annexin V-binding, decreased forward scatter and increased cytosolic Ca(2+) concentration but did not significantly modify ceramide formation. The effects of FTY720 were significantly blunted in the nominal absence of extracelluar Ca(2+). In conclusion, at toxic concentrations, FTY720 stimulates suicidal cell death, an effect at least partially due to stimulation of Ca(2+) entry.
The Serum and Glucocorticoid Inducible Kinases SGK1-3 Stimulate the Neutral Amino Acid Transporter SLC6A19
2010-01-01

The neutral amino acid transporter SLC6A19 (B(0)AT1) plays a decisive role in transport of neutral amino acids in the kidney and intestine. Recently, mutations in SLC6A19 were identified that result in severe neutral aminoaciduria known as Hartnup disorder. SLC6A19 expression and function is controlled by the brush-border angiotensin-converting enzyme 2 (ACE2). Beyond that the mechanisms regulating SLC6A19 function are unknown. The SLC6A19 sequence contains a conserved putative phosphorylation site for the serum and glucocorticoid inducible kinase isoforms SGK1-3, kinases known to regulate a variety of channels and transporters. The present study explored the role of SGK1-3 in the regulation of SLC6A19. As shown by two-electrode voltage clamp in the Xenopus oocyte expression system, leucine-induced currents in SLC6A19 expressing oocytes were activated by the protein kinases SGK1-3. The putative phosphorylation site on the transporter is not essential for SLC6A19 regulation by the kinases. As determined by quantitative immunoassay and electrophysiology, the kinases increase SLC6A19 currents by increasing the cell surface expression of the protein without altering the affinity of the carrier. Following inhibition of carrier insertion into the cell membrane by treatment with brefeldin A (BFA), the leucine-induced current declined significantly slower in Xenopus oocytes expressing SLC6A19 together with SGK1 than in oocytes expressing SLC6A19 alone, a finding pointing to SGK-mediated transporter stabilization in the plasma membrane. Coexpression of ACE2 markedly increased leucine-induced currents in SLC6A19 expressing oocytes that were further enhanced by SGK1-3 kinases. In conclusion, SGK isoforms are novel potent stimulators of SLC6A19 and may thus participate in the regulation of neutral amino acid transport in vivo.
The archaeological context of the Iwo Eleru cranium from Nigeria and preliminary results of new morphometric studies
2010-01-01

The Iwo Eleru skeleton was excavated from the rock shelter of this name in 1965 by Thurstan Shaw and his team. This contracted burial was found in a level with Late Stone Age (LSA) artefacts, and a radiocarbon determination on associated charcoal gave an (uncorrected) age of 11,200 ± 200 BP. The excavators went to considerable trouble to satisfy themselves that the specimen was in situ. There is no occupation prior to the LSA and only slight indications of a subsequent “iron age” occupation. Significant human burials have since been excavated elsewhere in West Africa (notably at Shum Laka and Gobero) but Iwo Eleru so far retains its status as the earliest known such burial in the region. The poorly preserved skeleton was of an adult and probably male individual, and the skull was reconstructed and studied by Brothwell. He linked the skull to recent West African populations, but he recognized that its lower vault and frontal profile were unusual. He also supplied cranial data for a Principal Components Analysis performed by Peter Andrews, and noted that this placed the specimen apart from recent African samples. Stringer included the Iwo Eleru cranium in univariate and multivariate (Canonical Variates, Generalised Distance) analyses for his doctoral thesis, completed in 1974. His results highlighted apparent archaic aspects in the specimen in its long and rather low cranial shape, and although modern overall, it also resembled fossils such as Omo Kibish 2 and Ngandong in certain respects. New studies using a primary replica of Brothwell’s reconstruction have now been carried out by Harvati, employing geometric morphometrics to generate PCA, CVA, Procrustes Distance and Minimum Spanning Tree analyses of the specimen. The new morphometric studies establish the relatively archaic shape of the vault, and confirm that this Late Stone Age individual was markedly different from succeeding populations. The results highlight our present relative lack of knowledge concerning the identity of the manufacturers of LSA artefacts in West Africa and other parts of the continent.
Monensin Induced Suicidal Erythrocyte Death
2010-01-01

Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or isosmotic cell shrinkage leading to increase of cytosolic Ca(2+) concentration. Eryptosis is further stimulated by the K(+) ionophore valinomycin, which leads to exit of KCl and osmotically obliged water, or by energy (glucose) depletion, which compromises the function of the Na(+)/K(+) ATPase thus increasing cytosolic Na(+) concentration. The present study explored whether the Na(+) ionophore monensin affects erythrocyte cell volume and eryptosis. The cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca(2+) concentration from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Within 24 hours, exposure to monensin (0.1-10 microg/ml) significantly increased forward scatter, cytosolic Ca(2+) concentration and annexin V-binding. Glucose depletion was followed by decreased forward scatter and increased cytosolic Ca(2+) concentration and annexin V-binding. The effect on forward scatter was partially reversed, the effect on cytosolic Ca(2+) concentration and annexin V binding augmented by additional treatment with monensin. In conclusion, monensin dissociates the alterations of cell membrane and cell volume in suicidal erythrocyte death.
Quantification and Negation in Event Semantics
2010-01-01

Recently, it has been claimed that event semantics does not go well together with quantification, especially if one rejects syntactic, LF-based approaches to quantifier scope. This paper shows that such fears are unfounded, by presenting a simple, variable-free framework which combines a Neo-Davidsonian event semantics with a type-shifting based account of quantifier scope. The main innovation is that the event variable is bound inside the verbal denotation, rather than at sentence level by existential closure. Quantifiers can then be interpreted in situ. The resulting framework combines the strengths of event semantics and type-shifting accounts of quantifiers and thus does not force the semanticist to posit either a default underlying word order or a syntactic LF-style level. It is therefore well suited for applications to languages where word order is free and quantifier scope is determined by surface order. As an additional benefit, the system leads to a straightforward account of negation, which has also been claimed to be problematic for event-based frameworks.
Planetary migration in resonance : the question of the eccentricities
2010-01-01

The formation of resonant planets pairs in exoplanetary systems involves planetary migration inside the protoplanetary disc: an inwards migrating outer planet captures in Mean Motion Resonance an inner planet. During the migration of the resonant pair of planets, the eccentricities are expected to rise excessively, if no damping mechanism is applied on the inner planet. We express the required damping action to match the observations, and we show that the inner disk can play this role. This result applies for instance to the system GJ 876: we reproduce the observed orbital elements through a fully hydrodynamical simulation of the evolution of the resonant planets.
Liver fat content determined by magnetic resonance imaging and spectroscopy
2010-01-01

Hepatic steatosis as the most prevalent liver disorder can either be related to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). In both conditions, hepatocytes excessively accumulate fat-containing vacuoles within their cytoplasm, which is the key histological feature. In contrast to ALD, NAFLD is commonly associated with metabolic syndrome, obesity and insulin resistance. To determine increased liver fat content, liver biopsy is currently considered the gold standard. Besides the invasive technique, various other non-invasive techniques have been developed, such as ultrasound, computed tomography (CT), magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) based methods. Among these techniques, ultrasound and CT provide only qualitative information about hepatic steatosis, whereas MRS- or MRI-based methods are able to determine even small amounts of fat accurately. These non-invasive magnetic resonance techniques have already proven their great potential, especially in longitudinal and cross-sectional studies regarding various metabolic conditions and medical treatment regimens. In this review, the most common, non-invasive MRS/MRI techniques for assessment of intrahepatic lipid content are described with their inherent advantages and limitations.
Riboswitch-mediated control of gene expression in eukaryotes
2010-01-01

The discovery of metabolite-sensing RNA domains with gene regulatory functions, so-called riboswitches, has greatly expanded our view of the structural and functional complexity of RNA. Hitherto, more than 20 distinct riboswitch classes have been identified, which respond to a variety of small molecules and perform sophisticated gene regulatory tasks. Riboswitches are typically positioned in the 5' untranslated region of bacterial mRNAs, where they control gene expression by transcriptional or translational attenuation. However, the recent investigation of additional riboswitch classes has revealed a more complex repertoire of regulatory mechanisms. This also includes splicing control in filamentous fungi, green algae and higher plants by thiamin pyrophosphate-binding riboswitches, the only class of metabolite-sensing RNAs identified in eukaryotes so far. All eukaryotic riboswitches characterized to date modulate, in a first step, splicing, but the downstream processes under control vary fundamentally among different species further highlighting the versatility of this gene regulatory mechanism.
Pathway-Targeted Pharmacogenomics of CYP1A2 in Human Liver
2010-01-01

The human drug metabolizing cytochrome P450 (CYP) 1A2, is one of the major P450 isoforms contributing by about 5-20% to the hepatic P450 pool and catalyzing oxidative biotransformation of up to 10% of clinically relevant drugs including clozapine and caffeine. CYP1A2 activity is interindividually highly variable and although twin studies have suggested a high heritability, underlying genetic factors are still unknown. Here we adopted a pathway-oriented approach using a large human liver bank (n = 150) to elucidate whether variants in candidate genes of constitutive, ligand-inducible, and pathophysiological inhibitory regulatory pathways may explain different hepatic CYP1A2 phenotypes. Samples were phenotyped for phenacetin O-deethylase activity, and the expression of CYP1A2 protein and mRNA was determined. CYP1A2 expression and function was increased in smokers and decreased in patients with inflammation and cholestasis. Of 169 SNPs in 17 candidate genes including the CYP1A locus, 136 non-redundant SNPs with minor allele frequency >5% were analyzed by univariate and multivariate methods. A total of 13 strong significant associations were identified, of which 10 SNPs in the ARNT, AhRR, HNF1α, IL1β, SRC-1, and VDR genes showed consistent changes for at least two phenotypes by univariate analysis. Multivariate linear modeling indicated that the polymorphisms and non-genetic factors together explained 42, 38, and 33% of CYP1A2 variation at activity, protein and mRNA levels, respectively. In conclusion, we identified novel trans-associations between regulatory genes and hepatic CYP1A2 function and expression, but additional genetic factors must be assumed to explain the full extent of CYP1A2 heritability.
Performance of 36 Different Weight Estimation Formulae in Fetuses with Macrosomia
2010-01-01

&lt;i&gt;Introduction:&lt;/i&gt; The aim of this retrospective clinical study was to compare the accuracy of 36 commonly used weight estimation formulae in macrosomic fetuses. &lt;i&gt;Material and Methods:&lt;/i&gt; Ultrasound estimation of fetal weight (FW) was carried out within 7 days up to delivery in 350 singleton fetuses with a birth weight (BW) of ≧4,000 g. The accuracy of the different formulae for FW estimation was compared by, firstly, the mean percentage (MPE) and mean absolute percentage error (MAPE), secondly, by the frequency distribution of differences between estimated FW and fetal BW, and thirdly by comparing detection and false positive rates in screening for fetuses with a BW of 4,000, 4,300 and 4,500 g or more. &lt;i&gt;Results:&lt;/i&gt; MPE ranged from –62.2 to 9.6% and was closest to 0 with the Hart formula. With 12 of 36 weight estimation formulae, MAPE was 10% or less, and was smallest with the Hart formulae (3.9%). The mean detection rate among all formulae for fetuses with a BW ≧4,000, ≧4,300 and ≧4,500 g was 29, 24 and 22%, respectively, and the false positive rate was 12% (for ≧4,300 g) and 7% (≧4,500 g). &lt;i&gt;Discussion:&lt;/i&gt; Some formulae showed advantages as far as mean and absolute percentage errors were concerned, but none reached a detection rate and false positive rate for fetuses ≧4,500 g that could lead to clinical recommendation.
Solid state metathesis reactions as a conceptual tool in the synthesis of new materials
2010-01-01

Solid state metathesis reactions can be used in the syntheses of inorganic solids and for strategic design of novel, eventually thermally labile materials. An explorative study of solid state metathesis reactions is presented for a number of examples, including syntheses of nitridoborates, carbodiimides, tetracyanoborates, tetracyanamidosilicates, carbon-nitride materials, and a number of other exciting compounds. This unique type of reaction is very efficient because it uses the intrinsic energy of reaction partners being involved. Desired compositions are achieved by appropriate starting materials and their relative amounts being combined into a solid state metathesis reaction. Reactions can be controlled through the heating-up procedure and by using a reactive flux, which may lower the ignition temperature of a reaction mixture and promote crystal growth of products.
On the possibilities of hard X-ray imaging with high spatio-temporal resolution using polychromatic synchrotron radiation
2010-01-01

Time-resolved imaging with penetrating radiation has an outstanding scientific value but its realisation requires a high density of photons as well as corresponding fast X-ray image detection schemes. Bending magnets and insertion devices of third generation synchrotron light sources offer a polychromatic photon flux density which is high enough to perform hard X-ray imaging with a spatio-temporal resolution up to the μm-μs range. Existing indirect X-ray image detectors commonly used at synchrotron light sources can be adapted for fast image acquisition by employing CMOS-based digital high speed cameras already available on the market. Selected applications from life sciences and materials research underline the high potential of this high-speed hard X-ray microimaging approach.
Bayesian inference for generalized linear models for spiking neurons
2010-01-01

Generalized Linear Models (GLMs) are commonly used statistical methods for modelling the relationship between neural population activity and presented stimuli. When the dimension of the parameter space is large, strong regularization has to be used in order to fit GLMs to datasets of realistic size without overfitting. By imposing properly chosen priors over parameters, Bayesian inference provides an effective and principled approach for achieving regularization. Here we show how the posterior distribution over model parameters of GLMs can be approximated by a Gaussian using the Expectation Propagation algorithm. In this way, we obtain an estimate of the posterior mean and posterior covariance, allowing us to calculate Bayesian confidence intervals that characterize the uncertainty about the optimal solution. From the posterior we also obtain a different point estimate, namely the posterior mean as opposed to the commonly used maximum a posteriori estimate. We systematically compare the different inference techniques on simulated as well as on multi-electrode recordings of retinal ganglion cells, and explore the effects of the chosen prior and the performance measure used. We find that good performance can be achieved by choosing an Laplace prior together with the posterior mean estimate.
Glucocorticoid‐Induced TNFR‐Related (GITR) Protein and Its Ligand in Antitumor Immunity: Functional Role and Therapeutic Modulation
2010-01-01

The ability of the tumor necrosis factor receptor (TNFR) family member GITR to modulate immune responses has been the subject of multiple studies. Initially thought to be critically involved in governing functions of regulatory T cells, GITR and its ligand GITRL have meanwhile been found to modulate the reactivity of various different cell types and to influence a broad variety of immunological conditions including the immune response against tumors. Not only GITR, but also GITRL is capable of transducing signals, and the consequences of GITR‐GITRL interaction may vary among different effector cell types, differ upon signal transduction via the receptor, the ligand, or both, depend on the level of an ongoing immune response, and even differ among mice and men. In this paper, we address available data on GITR and its ligand in immune responses and discuss the role and potential therapeutic modulation of this molecule system in antitumor immunity.
German Firms in Service Trade
2010-01-01

We provide firm-level evidence concerning four key facts of services trade in Germany. First, not only firms classified as service firms, but firms from all industries export and import services. Second, service trade patterns are fairly similar to those in goods trade. Most notably, service trade is dominated by a few large firms that serve many countries, sell several service products, and often export and import services. Differences in firms' trade values are the result from differences in all three margins of trade. Third, there is a strong concentration of firms on one core market and service. Fourth, the patterns are surprisingly similar for services exports and imports. JEL-Classifications: D21, F14, L80