julilili42/papers huggingface dataset:
Tracking Adult Neovascularization during Ischemia and Inflammation Using Vegfr2-LacZ Reporter Mice
2008-01-01

The vascular endothelial growth factor/vascular endothelial growth factor receptor 2 (VEGF/VEGFR-2) signal transduction system plays a key role during embryonic vascular development and adult neovascularization. In contrast to many endothelial genes, &lt;i&gt;VEGFR-2&lt;/i&gt; is expressed at low levels in most adult vessels but is strongly upregulated during neovascularization, leading to a pro-angiogenic response. Here, we analyzed the activity of regulatory sequences of the murine &lt;i&gt;Vegfr2&lt;/i&gt; gene during neovessel formation in vivo under ischemic and inflammatory conditions. Hindlimb ischemia was induced in transgenic mice, expressing the &lt;i&gt;LacZ&lt;/i&gt; reporter gene under the control of &lt;i&gt;Vegfr2&lt;/i&gt; promoter/enhancer elements. Most vessels in the ischemic muscle tissue showed strong endothelium-specific reporter gene expression, whereas nearly no &lt;i&gt;LacZ&lt;/i&gt;-expressing capillaries were observed in untreated control tissue. Cutaneous punch wounds were created to induce angiogenesis under inflammatory conditions, leading to robust &lt;i&gt;LacZ&lt;/i&gt; expression in the majority of the blood vessels in the wound tissue. Since the cornea is physiologically avascular, the functionality of these promoter/enhancer elements exclusively in newly formed vessels was confirmed using the cornea micropocket assay. Taken together, our results show that these &lt;i&gt;Vegfr2&lt;/i&gt; regulatory elements are active during adult neovessel formation in general. Therefore, these sequences may prove to be valuable targets for novel endothelium-specific anti-angiogenic as well as pro-angiogenic treatment strategies. They may especially allow directing therapeutic gene expression to sites of adult neovascularization. Moreover, the Vegfr2/LacZ reporter mice represent a powerful model to generally analyze the transcriptional control mechanisms involved in the induction of &lt;i&gt;Vegfr2&lt;/i&gt; expression during adult neovascularization.
Stimulation of Eryptosis by Cadmium Ions
2008-01-01

Cadmium ions are known to trigger apoptosis. Erythrocytes may similarly undergo suicidal death or eryptosis, which is characterized by exposure of phosphatidylserine at the erythrocyte surface. As macrophages are equipped with phosphatidylserine receptors, they bind, engulf and degrade phosphatidylserine exposing cells. Cellular mechanisms known to trigger cell membrane phospholipid scrambling include increased cytosolic Ca(2+) activity and activation of a sphingomyelinase with formation of ceramide. The present experiments were performed to explore whether cadmium ions (Cd(2+)) trigger phosphatidylserine exposure of erythrocytes and to possibly identify underlying mechanisms. Phosphatidylserine exposure was estimated from annexin V-binding as determined in fluorescence activated cell sorting (FACS) analysis. Exposure to Cd(2+) (>or= 5.5 microM Cd(2+)) indeed significantly increased annexin V-binding. This effect was paralleled by erythrocyte shrinkage as apparent from the decrease of forward scatter in FACS analysis. According to Fluo3 fluorescence, Cd(2+) increased the entry of Ca(2+) into erythrocytes. According to antibody binding, Cd(2+) did not stimulate the formation of ceramide. In the nominal absence of extracellular Ca(2+) and in the presence of cation channel inhibitor amiloride the effects of Cd(2+) on erythrocyte phosphatidylserine exposure and forward scatter were blunted. In conclusion, in human erythrocytes Cd(2+) stimulates entry of Ca(2+), which activates Ca(2+)-sensitive K(+) channels leading to erythrocyte shrinkage and triggers Ca(2+)-sensitive erythrocyte membrane scrambling leading to phosphatidylserine exposure.
Lipopeptides in the Triggering of Erythrocyte Cell Membrane Scrambling
2008-01-01

Sepsis is paralleled by anemia, an effect partially resulting from eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Pathogen-induced eryptosis may partially result from interaction of bacterial cell wall components such as lipoproteins with the erythrocyte cell membrane. The present study explored, whether the synthetic lipopeptide Pam3CSK4 mimicking the acylated amino terminus of bacterial lipoproteins triggers eryptosis. According to annexin-V-binding in FACS analysis, Pam3CSK4 (1 microg/ml) stimulated phosphatidylserine exposure, an effect significantly blunted in the nominal absence of Ca(2+). According to Fluo3 fluorescence, Pam3CSK4 increased cytosolic Ca(2+) activity and moderately stimulated erythrocytic ceramide formation, both major triggers of eryptosis. In conclusion, bacterial lipoproteins participate in the stimulation of erythrocyte cell membrane scrambling by bacterial cell wall components. Thus, lipoprotein-dependent suicidal erythrocyte death may contribute to the pleotropic effects of sepsis.
A High Specificity and Affinity Interaction with Serum Albumin Stimulates an Anion Conductance in Malaria-Infected Erythrocytes
2008-01-01

The intraerythrocytic development of P. falciparum induces New Permeability Pathways (NPP) in the membrane of the parasitized erythrocyte which provide the parasite with nutrients, adjust the erythrocyte electrolyte composition to the needs of the parasite, and dispose of metabolic waste products and osmolytes. Patch-clamp recordings identified inwardly and outwardly rectifying (OR) anion conductances in the host erythrocyte membrane as electrophysiological correlate of the NPP. The OR conductance is regulated by serum. Here we show that serum albumin (SA) stimulated OR-generated Cl(-) and lactate outward currents with an EC(50) of approximately 100 nM while other proteins such as ovalbumin or casein did not. The stimulatory efficacy did not differ between fatty acid free bovine SA and recombinant human SA and disruption of the SA tertiary structure abolished the effect suggesting that intact SA protein and not other bound factors interact with the erythrocyte membrane. Taken together, the data indicate a high affinity and specificity interaction of native SA with the parasitized erythrocytes which might underlie the observed dependence of P. falciparum growth in vitro on SA.
Immunological Potential ofHelix vulgarisandRapana venosaHemocyanins
2008-01-01

A new hemocyanin was isolated from the hemolymph of garden snails Helix vulgaris, composed of two isoforms, HvH1 and HvH2 separated on an ion exchange column DEAE-Sepharose 6CL. Structural and immunological properties of Helix vulgaris hemocyanin were studied in comparison with molluscan Hcs Rapana venosa and Megathura crenulata. The possibility of using HvH and RvH as carriers of small molecules (haptens) in immunizing protocols was studied in comparison with KLH, which is a widely used, highly immunogenic carrier protein. By using HvH as a carrier of the well-known hapten TNBS (2,4,6-trinitrobenzene sulfonic acid), an increasing with time production of hapten-specific TFN-gamma was detected in splenocyte cultures of mice, which lasted longer than in case of KLH and RvH carriers. Also, use of HvH or RvH as a carrier of the hapten ProT alpha[101-109] (i.e., the synthetic C-terminal fragment of the poorly immunogenic protein prothymosin alpha) showed that antisera of higher titres than that of the control conjugate (ProT alpha[101-109]-KLH) were obtained immediately after the second bleeding. HvH and RvH may prove to be useful for the development of new antiviral, antibacterial and antitumor vaccines, since they seem to launch strong and specific immune response against the conjugated antigens.
Pump and Channel K<sup>&plus;</sup> (Rb<sup>&plus;</sup>) Fluxes in Apoptosis of Human Lymphoid Cell Line U937
2008-01-01

Ouabain-sensitive (OS) and -resistant (OR) Rb(+) influx was examined in three sublines of U937 cells to compare alterations of K(+) channel permeability and the Na(+),K(+)-ATPase pump leading to the shift in ion and water balance during apoptosis induced by 0.2 and 1microM staurosporine (STS) for 4-5 h. Cell K(+), Rb(+), Na(+) and Cl(-) content was determined by flame photometry and (36)Cl distribution. Changes in cell water content were monitored by measurement of buoyant cell density and distribution of [(3)H]-glycerol or 3-O-methyl-D-[(3)H]glucose. Apoptosis was detected by DNA flow cytometry and light microscopy of the native cells stained with acridine orange. Treatment with 0.2 microM STS for 5 hours led to mild apoptosis with 10-13 % cell dehydration and either moderate increase of channel mediated Rb(+) influx without significant changes in the pump activity or moderate decrease of pump Rb(+) influx without significant change of channel influx, depending on the cell line used. Treatment with 1 microM STS was followed by 18-23 % cell dehydration, a decrease of the pump activity and a small or insignificant increase in the OR Rb(+) influx in all studied sublines. It is concluded that moderate apoptotic cell shrinkage may be associated with both an increase in K(+) channel permeability and inhibition of the pump whereas more remarkable shrinkage occurs presumably due to inhibition of the pump.
Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis
2008-01-01

The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for protein extraction and histology. C-terminal telopeptide of type III collagen (CTX-II), CTX-I and hydroxyproline were measured in protein extracts. Matrix metalloproteinase (MMP)-2 and -9 activity was evaluated by gelatinase zymography and joint pathology was visualized by histology and immunohistochemistry. The results showed that levels of CTX-II were significantly increased in anterior cruciate ligament transection (ACLT)-operated compared with sham-operated knee joints on days 7 and 28, whereas the levels of hydroxyproline and CTX-I epitopes showed no difference. MMP activity was slightly increased in ACLT-operated joints. The CTX-II epitope was highly expressed and co-localized to damaged articular cartilage in ACLT-operated joints. We have therefore demonstrated an increased type II collagen degradation in knees after surgical induction of OA, and propose assessment of collagen degradation epitopes as a quantitative measure of cartilage damage.
Angiopoietin-2 Deficiency Decelerates Age-Dependent Vascular Changes in the Mouse Retina
2008-01-01

Retinae of aged humans show signs of vascular regression. Vascular regression involves a mismatch between Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) expression. We used heterozygous Ang-2 deficient (Ang2LacZ) mice to evaluate murine retinal vascular changes and gene expression of growth factors. Vascular changes were assessed by quantitative retinal morphometry and gene expression levels of growth factors were measured by quantitative PCR. The numbers of endothelial cells and pericytes did not change in the Ang2LacZ retinae with age, whereas they decreased throughout the age spectrum studied in the wild type retinae. Moreover, vascular regression significantly decelerated in the heterozygous Ang2LacZ retinae (200% to 1 month), while the formation of acellular capillaries was significantly increased at 13 months in the wild type retinae (340% to 1 month). Gene expression analysis revealed that VEGF, Ang-1, PDGF-B and Ang2 mRNA levels were decreased in the wild type retinae at 9 month of age. However, the decrease of Ang-2 was smaller compared with other genes. While VEGF levels dropped in wild type mice up to 60% compared to 1 month, VEGF increased in heterozygous Ang-2 deficient retinae at an age of 9 months (141% to 1 month). Similarly, Ang-1 levels decreased in wild type mice (45% to 1 month), but remained stable in Ang2LacZ mice. These data suggest that Ang-2 gene dose reduction decelerates vasoregression in the retina with age. This effect links to higher levels of survival factors such as VEGF and Ang-1, suggesting that the ratio of these factors is critical for capillary cell survival.
Diminished Expression of Apical Sodium-Dependent Bile Acid Transporter in Gallstone Disease Is Independent of Ileal Inflammation
2008-01-01

&lt;i&gt;Background:&lt;/i&gt; Non-obese gallstone patients exhibit a diminished expression of apical sodium-dependent bile acid transporter (ASBT) in terminal ileum. Crohn’s ileitis demonstrates a significant downregulation of this transporter. &lt;i&gt;Aim:&lt;/i&gt; To test whether subclinical ileal inflammation contributes to gallstone disease. &lt;i&gt;Methods:&lt;/i&gt; Biopsies from terminal ileum of female subjects with gallstone disease (n = 7), active Crohn’s disease (n = 17) and controls (n = 22) were investigated. mRNA expression of ASBT, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-8, c-jun and c-fos was measured. c-jun and c-fos protein levels were determined and hematoxylin and eosin staining was applied for ileal histology. &lt;i&gt;Results:&lt;/i&gt; ASBT expression was comparably low both in gallstone (47% of controls, p = 0.0093) and Crohn’s disease (42% of controls, p = 0.0008). In gallstone disease there was a non-significant trend towards elevated TNF-α and IL-1β, but all cytokines were increased in active Crohn’s disease. c-jun and c-fos were slightly diminished in patients with gallstones. Neither cytokines nor transcription factors correlated significantly with ASBT. The gallstone-associated ileal biopsies exhibited no histological inflammation. &lt;i&gt;Conclusion:&lt;/i&gt; Although the expression of ASBT was similarly diminished in both gallstone and Crohn’s disease, subclinical ileal inflammation does not appear to be relevant in gallstone patients. The mechanisms of transcriptional repression of ASBT in both diseases are apparently different.
Role of Serum- and Glucocorticoid-Inducible Kinase SGK1 in Glucocorticoid Regulation of Renal Electrolyte Excretion and Blood Pressure
2008-01-01

&lt;i&gt;Background/Aims:&lt;/i&gt; The serum- and glucocorticoid-inducible kinase SGK1 was originally cloned as a glucocorticoid-regulated gene and later as a transcriptional target for mineralocorticoids. SGK1 regulates channels and transporters including the renal Na&lt;sup&gt;+&lt;/sup&gt; channel ENaC. It contributes to mineralocorticoid regulation of renal Na&lt;sup&gt;+&lt;/sup&gt; excretion and salt appetite. The present study explored the contribution of SGK1 to effects of glucocorticoids on mineral and electrolyte metabolism. &lt;i&gt;Methods:&lt;/i&gt; SGK1-knockout mice (&lt;i&gt;sgk1&lt;/i&gt;&lt;sup&gt;–/–&lt;/sup&gt;) and their wild-type littermates (&lt;i&gt;sgk1&lt;/i&gt;&lt;sup&gt;+/+&lt;/sup&gt;) were analyzed in metabolic cages with or without treatment for 14 days with dexamethasone (3 mg/kg b.w., i.p.). Blood pressure was determined by the tail-cuff method. &lt;i&gt;Results:&lt;/i&gt; Prior to treatment fluid intake, urinary flow rate, urinary Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;, phosphate and Cl&lt;sup&gt;–&lt;/sup&gt; excretion, plasma electrolyte and glucose concentrations as well as blood pressure were similar in &lt;i&gt;sgk1&lt;/i&gt;&lt;sup&gt;–/–&lt;/sup&gt; and&lt;i&gt; sgk1&lt;/i&gt;&lt;sup&gt;+/+&lt;/sup&gt; mice. Dexamethasone did not significantly alter renal Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;, Cl&lt;sup&gt;–&lt;/sup&gt; and Ca&lt;sup&gt;2+&lt;/sup&gt; excretion but decreased plasma Ca&lt;sup&gt;2+&lt;/sup&gt; and phosphate concentration in &lt;i&gt;sgk1&lt;/i&gt;&lt;sup&gt;+/+&lt;/sup&gt; mice. The effect on Ca&lt;sup&gt;2+&lt;/sup&gt; was significantly augmented and the effect on phosphate significantly blunted in &lt;i&gt;sgk1&lt;/i&gt;&lt;sup&gt;–/–&lt;/sup&gt; mice. Dexamethasone significantly increased fasting blood glucose concentrations in both genotypes. Dexamethasone increased blood pressure in &lt;i&gt;sgk1&lt;/i&gt;&lt;sup&gt;+/+&lt;/sup&gt; mice, an effect significantly blunted in &lt;i&gt;sgk1&lt;/i&gt;&lt;sup&gt;–/–&lt;/sup&gt; mice. &lt;i&gt;Conclusions:&lt;/i&gt; The present observations disclose SGK1-sensitive glucocorticoid effects on calcium-phosphate metabolism and blood pressure.
Experimental and theoretical evaluation of surface plasmon-coupled emission for sensitive fluorescence detection
2008-01-01

Surface plasmon-coupled emission (SPCE) is a phenomenon whereby the light emitted from a fluorescent molecule can couple into the surface plasmon of an adjacent metal layer, resulting in highly directional emission in the region of the surface plasmon resonance (SPR) angle. In addition to high directionality of emission, SPCE has the added advantage of surface selectivity in that the coupling diminishes with increasing distance from the surface. This effect can be exploited in bioassays whereby a fluorescing background from the sample can be suppressed. We have investigated, both theoretically and experimentally, the SPCE effect for a Cy5-spacer-Ag layer system. Both the angular dependence of emission and the dependence of SPCE emission intensity on Cy5-metal separation were investigated. It is demonstrated that SPCE leads to lower total fluorescence signal than that obtained in the absence of a metal layer. This is the first experimental verification of the reduction in SPCE intensity compared to the metal-free case. Our results are in a good agreement with theoretical models. The validation of the theoretical model provides a basis for optimizing biosensor platform performance, particularly in the context of the advantages offered by SPCE of highly directional emission and surface selectivity.
SGK1-Dependent Upregulation of Connective Tissue Growth Factor by Angiotensin II
2008-01-01

Angiotensin II has previously been shown to trigger fibrosis, an effect involving connective tissue growth factor (CTGF). The signaling pathways linking angiotensin II to CTGF formation are, however, incompletely understood. A gene highly expressed in fibrosing tissue is the serum- and glucocorticoid-inducible kinase SGK1. The present study explored whether SGK1 is transcriptionally regulated by angiotensin II and participates in the angiotensin II-dependent regulation of CTGF expression. To this end, experiments have been performed in human kidney fibroblasts and mouse lung fibroblasts from gene-targeted mice lacking SGK1 (sgk1&lt;sup&gt;–/–&lt;/sup&gt;) and their wild-type littermates (sgk1&lt;sup&gt;+/+&lt;/sup&gt;). In human renal fibroblasts, SGK1 and CTGF protein expression were enhanced by angiotensin II (10 n&lt;i&gt;M&lt;/i&gt;) within 4 h. In sgk1&lt;sup&gt;+/+&lt;/sup&gt; mouse fibroblasts, SGK1 transcript levels were significantly increased after 4 h of angiotensin II treatment. Angiotensin II stimulated both transcript and protein abundance of CTGF in fibroblasts from sgk1&lt;sup&gt;+/+&lt;/sup&gt; mice, effects significantly blunted in fibroblasts of sgk1&lt;sup&gt;–/–&lt;/sup&gt; mice. In conclusion, angiotensin II stimulates the expression of SGK1, which is in turn required for the stimulating effect of angiotensin II on the expression of CTGF. Thus, SGK1 presumably contributes to the profibrotic effect of angiotensin II.
TuLiPA
2008-01-01

In this paper, we present an open-source parsing environment (Tübingen Linguistic Parsing Architecture, TuLiPA) which uses Range Concatenation Grammar (RCG) as a pivot formalism, thus opening the way to the parsing of several mildly context-sensitive formalisms. This environment currently supports tree-based grammars (namely Tree-Adjoining Grammars (TAG) and Multi-Component Tree-Adjoining Grammars with Tree Tuples (TT-MCTAG)) and allows computation not only of syntactic structures, but also of the corresponding semantic representations. It is used for the development of a tree-based grammar for German.
Pathfinder: XQuery Off the Relational Shelf.
2008-01-01

The Pathfinder project makes inventive use of relational database technology—originally developed to process data of strictly tabular shape—to construct efficient database-supported XML and XQuery processors. Pathfinder targets database engines that implement a set-oriented mode of query execution: many off-the-shelf traditional database systems make for suitable XQuery runtime environments, but a number of off-beat storage back-ends fit that bill as well. While Pathfinder has been developed with a close eye on the XQuery semantics, some of the techniques that we will review here will be generally useful to evaluate XQuery-style iterative languages on database back-ends. 1 The Rectangularization of XQuery: Purely Relational XML Processing If you zoom back in time to dig for the semantic roots of XQuery [5], you will find that the language’s core construct, the for–let–where–order by–return (FLWOR) block is one particular incarnation of a very general idea: the comprehension [26]. Many language-related concepts may be uniformly understood in comprehension form, but comprehensions provide a particularly concise and elegant way to express iteration over collections of objects—in the case of XQuery: finite, ordered sequences of XML nodes and atomic values (or items) [1]. Any program or query expressed in comprehension form is subject to a number of useful equivalencepreserving
Endothelial NO-Synthase Intron 4 Polymorphism is Associated with Disturbed In Vivo Nitric Oxide Production in Individuals Prone to Type 2 Diabetes
2008-01-01

Insulin resistance, as well as vascular disease, both share a relevant genetic background taking the influence of a positive family history of these disorders. On the other hand, insulin resistance is associated with a proatherosclerotic disturbance in nitric oxide dependent vasodilation, probably contributing to the link between these two disorders. We examined the association between nitric oxide dependent vasodilation (measured with high resolution ultrasound at 13 MHz) and three relevant NO-synthase (eNOS)-polymorphisms in 200 insulin resistant subjects participating in the Tuebinger Lifestyle Intervention Program (TULIP). This study revealed that carriers of the eNOS intron 4 polymorphism (aa 2.16%; ab 24.2%; bb 73.2%) show significantly worse endothelial, and thereby eNOS dependent vasodilation (p=0.03, multivariate ANOVA), as compared to wildtype carriers. The 5' UTR T-786C and the G894 T polymorphism did not show any influence on eNOS-activity. In subjects at increased risk to develop type 2 diabetes, the eNOS intron 4 polymorphism is independently associated with endothelial function as indicated by disturbed endothelial NO production. Due to the high prevalence and the relatively strong effect, this polymorphism might help to identify subjects at increased risk for atherosclerosis associated with overweight and insulin resistance.
Comparison between a linear versus a macrocyclic contrast agent for whole body MR angiography in a clinical routine setting
2008-01-01

The high diagnostic accuracy of gadobutrol in the clinical routine setting is of high interest as medical authorities (e.g. the European Agency for the Evaluation of Medicinal Products) recommend macrocyclic contrast agents especially to be used in patients with renal failure or dialysis.