julilili42/papers huggingface dataset:
Hypericin: a promising fluorescence marker for differentiating between glioblastoma and neurons in vitro.
2005-12-01

The naturally occurring photosensitizer, hypericin, with its high quantum yield of singlet oxygen photogeneration was studied for its ability to differentiate between glioblastoma cells and fetal rat neurons using fluorescence microscopy. Eight human glioma cell lines and twelve primary human glioma cell cultures were compared to human astrocytes and cerebellar granule neurons after incubation with 20 microM hypericin for 5-120 min. Photobleaching effects have been studied by exposing the cell lines to 100 msec of excitation light (510-550 wavelength). Mainly, perinuclear hypericin staining was detected. Neurons can be differentiated from glioblastoma cell lines and astrocytes by a lower fluorescence intensity (Tukey-Kramer HSD test, p < 0.0001). Therefore, hypericin seems to be a promising substance for the photodynamic therapy of malignant brain tumors.
New phenotypes of functional expression of the mKir2.1 channel in potassium efflux‐deficient Saccharomyces cerevisiae strains
2005-12-01

Abstract The functional expression of the mouse Kir2.1 potassium channel in yeast cells lacking transport systems for potassium and sodium efflux ( ena1‐4 Δ nha1 Δ) resulted in increased cell sensitivity to high external concentrations of potassium. The phenotype depended on the level of Kir2.1 expression and on the external pH. The activity of Kir2.1p in the yeast cells was almost negligible at pH 3.0 and the highest at pH 7.0. Kir2.1p was permeable for both potassium and rubidium cations, but neither sodium nor lithium were transported via the channel. Measurements of the cation contents in cells confirmed the higher concentration of potassium in cells with Kir2.1p. Specific inhibition of the mKir2.1 channel activity by Ba 2+ cations was observed. The use of a mutant strain lacking both potassium efflux and uptake transporters ( ena1‐4 Δ nha1 Δ trk1 Δ trk2 Δ) enabled the monitoring of channel activity on two levels—the provision of the necessary amount of intracellular K + in media with low potassium concentrations, and simultaneously, the channel's contribution to cell potassium sensitivity in the presence of high external K + . This combination of mutations proved to be a new, sensitive and practical tool for characterizing the properties of heterologously expressed transporters mediating both the efflux and influx of alkali‐metal‐cations. Copyright © 2005 John Wiley &amp; Sons, Ltd.
Myasthenia gravis with MuSK antibodies
2005-12-01

<b>INTRODUCTION</b> Antibodies to the muscle acetylcholine receptor (AChR) are present in about 85% of patients with generalized myasthenia gravis, and 50% of patients with just ocular symptoms. However, up to 70% of the myasthenia patients without AChR antbodies, so called 'seronegative' myasthenia gravis, have antibodies to the muscle specific tyrosine kinase (MuSK). MuSK is another protein at the postsynaptic membrane of the neuromuscular junction, and plays a role in agrin-induced AChR clustering (Hoch <i>et al</i>. 2001). These patients may be difficult to recognize, and difficult to treat effectively. Here we describe four AChR antibody-negative/MuSK antibody-positive patients as examples. <b>THE CASES (SEE TABLE 1)</b> <b>Case 1</b> This patient had an age at onset and clinical presentation typical of myasthenia gravis but was difficult to treat. She was a 30-year old woman who developed diplopia, dysphagia and dysarthria during the third trimester of her first pregnancy. EMG showed a defect of neuromuscular
SIGNIFICANTLY IMPROVED PREDICTION OF SUBCELLULAR LOCALIZATION BY INTEGRATING TEXT AND PROTEIN SEQUENCE DATA
2005-12-01

Computational prediction of protein subcellular localization is a challenging problem. Several approaches have been presented during the past few years; some attempt to cover a wide variety of localizations, while others focus on a small number of localizations and on specific organisms. We present a comprehensive system, integrating protein sequence-derived data and text-based information. Itis tested on three large data sets, previously used by leading prediction methods. The results demonstrate that our system performs significantly better than previously reported results, for a wide range of eukaryotic subcellular localizations.
Democratic thought and practice in rural China
2005-12-01

Chinese democratization is usually thought of as a top-down process sponsored by a reform-minded government and liberal intellectuals. At the turn of the millennium, however, no such development is in sight. Only recently have Western scholars begun to look to the countryside for finding ‘sprouts of democracy’. This study explores village self-government as a possibility of making local political practices the foundation of an emerging rights consciousness that becomes increasingly abstract and finally transgresses into the national sphere. Central to the argument is the dynamic of the village moral economy that produces a common good and ‘collectivity’. These are serving as the pillars of all political claims that rise from the villages. In the process of appropriating an ongoing national discourse on political reform and democracy, China's peasants translate their entitlements derived from the moral economy of the village into rights, by way of informing a moral contract between them and authority. This contract may lay the ground for full-scale resistance, if the state and its cadres do not respond to the peasants' ‘rightful’ demands. However, if it is honoured it can reinforce trust and secure the current regime's legitimacy.
Signalling in Immune Cells
2005-12-01

A long-standing paradox in the study of T cell antigen recognition is that of the high specificity-low affinity TCR-MHCp interaction.The existence of multivalent TCRs could resolve this paradox because they can simultaneously improve the avidity observed for monovalent interactions and allow for cooperative effects.We have studied the stoichiometry of the TCR by Blue Native-gel electrophoresis and found that the TCR exists as a mixture of monovalent (abcedef2) and multivalent complexes with two or more ligand-binding TCRa/b subunits.The co-existence of monovalent and multivalent complexes was confirmed by electron microscopy after label-fracture of intact T cells, thus ruling out any possible artefact caused by detergent solubilization.We found that while at low antigen doses only the multivalent complexes become phosphorylated, both multivalent and monovalent TCRs are phosphorylated at higher doses.Thus, the multivalent TCRs could be responsible for sensing low concentrations of antigen, whereas the monovalent TCRs could be responsible for dose-response effects at high concentrations, conditions in which the multivalent TCRs are saturated.Thus, besides resolving TCR stoichiometry, these data can explain how T cells respond to a wide range of MHCp concentrations while maintaining high sensitivity.
Identification of a minimal peptide sequence of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties
2005-12-02

Aphrodite Kapurniotu, Jurgen Bernhagen, Wolfgang Fischle, Saul Teichberg, Wolfgang Voelter and Richard Bucala Physiologisch-chemisches Institut, Hoppe-Seylerstr. 4, D-72076 Tubingen, Germany; Universitat Stuttgart, Fraunhofer Institut, Nobelstr. 12, D-70569 Stuttgart, Germany; North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA; The Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA
HIF-1–dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia
2005-12-05

Extracellular adenosine (Ado) has been implicated as central signaling molecule during conditions of limited oxygen availability (hypoxia), regulating physiologic outcomes as diverse as vascular leak, leukocyte activation, and accumulation. Presently, the molecular mechanisms that elevate extracellular Ado during hypoxia are unclear. In the present study, we pursued the hypothesis that diminished uptake of Ado effectively enhances extracellular Ado signaling. Initial studies indicated that the half-life of Ado was increased by as much as fivefold after exposure of endothelia to hypoxia. Examination of expressional levels of the equilibrative nucleoside transporter (ENT)1 and ENT2 revealed a transcriptionally dependent decrease in mRNA, protein, and function in endothelia and epithelia. Examination of the ENT1 promoter identified a hypoxia inducible factor 1 (HIF-1)–dependent repression of ENT1 during hypoxia. Using in vitro and in vivo models of Ado signaling, we revealed that decreased Ado uptake promotes vascular barrier and dampens neutrophil tissue accumulation during hypoxia. Moreover, epithelial Hif1α mutant animals displayed increased epithelial ENT1 expression. Together, these results identify transcriptional repression of ENT as an innate mechanism to elevate extracellular Ado during hypoxia.
Reduced Cord Blood Immune Effector‐Cell Responsiveness Mediated by CD4+Cells Induced in Utero as a Consequence of PlacentalPlasmodium falciparumInfection
2005-12-05

To determine mechanisms of neonatal parasite antigen (Ag)-specific immune suppression associated with placental Plasmodium falciparum infection, we isolated cord blood mononuclear cells (CBMCs) from Gabonese neonates born to mothers with differing histories of P. falciparum infection and performed ex vivo and in vitro studies to evaluate immune regulatory activity. We found increased ex vivo percentages of CD4(+)CD25(hi) and CD4(+)CD25(+)CTLA-4(+) cells and increased interleukin (IL)-10 responses to parasite Ag in vitro in CBMCs from neonates born to mothers with placental P. falciparum infection at delivery. Depleting CBMCs of CD4(+)CD25(+) cells before cell culture led to the abrogation of parasite Ag-specific IL-10 responses, to enhanced interferon- gamma responses, and to enhanced expression of CD25 on CD8(+) T cells and of major histocompatibility complex class I and II on monocytes. These data demonstrate that parasite Ag-specific CD4(+) regulatory cells are generated in utero as a consequence of placental P. falciparum infection.
cAMP Is a Ligand for the Tandem GAF Domain of Human Phosphodiesterase 10 and cGMP for the Tandem GAF Domain of Phosphodiesterase 11
2005-12-06

N-terminal tandem GAF domains are present in 5 out of 11 mammalian phosphodiesterase (PDE) families. The ligand for the GAF domains of PDEs 2, 5, and 6 is cGMP, whereas those for PDEs 10 and 11 remained enigmatic for years. Here we used the cyanobacterial cyaB1 adenylyl cyclase, which has an N-terminal tandem GAF domain closely related to those of the mammalian PDEs, as an assay system to identify the ligands for the human PDEs 10 and 11 GAF domains. We report that a chimera between the PDE10 GAF domain and the cyanobacterial cyclase was 9-fold stimulated by cAMP (EC50= 19.8 microm), whereas cGMP had only low activity. cAMP increased Vmax in a non-cooperative manner and did not affect the Km for ATP of 27 microm. In an analogous chimeric construct with the tandem GAF domain of human PDE11A4, cGMP was identified as an allosteric activator (EC50 = 72.5 microm) that increased Vmax of the cyclase non-cooperatively 4-fold. GAF-B of PDE10 and GAF-A of PDE11A4 contain an invariant NKFDE motif present in all mammalian PDE GAF ensembles. We mutated the aspartates within this motif in both regions and found that intramolecular signaling was considerably reduced or abolished. This was in line with all data concerning GAF domains with an NKFDE motif as far as they have been tested. The data appeared to define those GAF domains as a distinct subclass within the >3100 annotated GAF domains for which we propose a tentative classification scheme.
BALLView: a tool for research and education in molecular modeling
2005-12-06

Abstract Summary: We present BALLView, a molecular viewer and modeling tool. It combines state-of-the-art visualization capabilities with powerful modeling functionality including implementations of force field methods and continuum electrostatics models. BALLView is a versatile and extensible tool for research in structural bioinformatics and molecular modeling. Furthermore, the convenient and intuitive graphical user interface offers novice users direct access to the full functionality, rendering it ideal for teaching. Through an interface to the object-oriented scripting language Python it is easily extensible. Availability: BALLView is an open source software and runs on all major platforms (Windows, MacOS X, Linux and most Unix flavors). It is available free of charge under the GNU Public License at Contact: amoll@bioinf.uni-saarland.de
Interactions of Bupivacaine with a Molecularly Imprinted Polymer in a Monolithic Format Studied by NMR
2005-12-06

A trimethylolpropane trimethacrylate-based monolith of dimensions carefully chosen to fit exactly in a standard 4-mm solid-state CP/MAS NMR rotor was photopolymerized and subsequently molecularly imprinted with bupivacaine using a grafting protocol with methacrylic acid and ethylene dimethacrylate as monomers. As no crushing or grinding of the monolith was necessary, additional unspecific surface area was not created. This procedure ascertains that differences observed between imprinted and nonimprinted polymers are due only to graft imprinted surfaces and give therefore better results in NMR spectroscopy due to less unspecific interactions between analyte and monolith. This improves the comparability to chromatographic evaluations where uncrushed monolithic columns are also used. To track interactions between analyte and stationary phase, the saturation transfer difference (STD) technique was applied on the polymer in the suspended state using the same solvent as in the chromatographic evaluation. This relatively new NMR method has to our knowledge not been used on chromatographic materials before. By using STD NMR on pristine monoliths, it was possible to measure large differences between the imprinted or nonimprinted polymers and the analyte indicating significant differences in the interaction mechanisms. These could be directly correlated with retention differences observed in chromatographic evaluations.
Amyloidogenesis of Islet Amyloid Polypeptide (IAPP)
2005-12-06

Our studies suggest that insoluble amyloid formation by IAPP follows kinetics that are consistent with a nucleation-dependent polymerization mechanism. Thus, IAPP amyloid formation can be accelerated by seeding with preformed IAPP amyloid fibrils. At the molecular level, IAPP amyloid formation was found to proceed via a conformational transition into hydrophobic β-sheet containing conformeric states. The transition into β-sheets could also be seeded by IAPP fibrils and proceeded via formation of a structured state with strongly solvent-exposed hydrophobic patches. This amyloid ogenic state was found to be populated in both the temperature-and the denaturant-induced denaturation pathways of IAPP and led to formation of insoluble amyloid fibrils. Concentration dependence CD studies suggested that the partly folded amyloidogenic state may form by self-association of partially unfolded IAPP. Based on these results and on the observed nucleation-dependent protein polymerization mechanism, we propose that partially unfolded IAPP and its self-associated forms may be in equilibrium with native or non-amyloidogenic IAPP conformers and act as early and soluble precursors of β-sheet and amyloid formation.
Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion
2005-12-07

Glucose depletion of erythrocytes leads to activation of Ca 2+ -permeable cation channels, Ca 2+ entry, activation of a Ca 2+ -sensitive erythrocyte scramblase, and subsequent exposure of phosphatidylserine at the erythrocyte surface. Ca 2+ entry into erythrocytes was previously shown to be stimulated by phorbol esters and to be inhibited by staurosporine and chelerythrine and is thus thought to be regulated by protein phosphorylation/dephosphorylation, presumably via protein kinase C (PKC) and the corresponding phosphoserine/threonine phosphatases. The present experiments explored whether PKC could contribute to effects of energy depletion on erythrocyte phosphatidylserine exposure and cell volume. Phosphatidylserine exposure was estimated from annexin binding and cell volume from forward scatter in fluorescence-activated cell sorter analysis. Removal of extracellular glucose led to depletion of cellular ATP, stimulated PKC activity, led to translocation of PKCα, enhanced serine phosphorylation of membrane proteins, decreased cell volume, and increased annexin binding, the latter effect being blunted but not abolished in the presence of 1 μM staurosporine or 50 nM calphostin C. The PKC stimulator phorbol-12-myristate-13-acetate (3 μM) and the phosphatase inhibitor okadaic acid (1–10 μM) mimicked the effect of glucose depletion and similarly led to translocation of PKCα and enhanced serine phosphorylation, increased annexin binding, and decreased forward scatter, the latter effects being abrogated by PKC inhibitor staurosporine (1 μM). Fluo-3 fluorescence measurements revealed that okadaic acid also enhanced erythrocyte Ca 2+ activity. The present observations suggest that protein phosphorylation and dephosphorylation via PKC and the corresponding protein phosphatases contribute to phosphatidylserine exposure and cell shrinkage after energy depletion.
Prediction of Partitioning between Complex Organic Mixtures and Water:  Application of Polyparameter Linear Free Energy Relationships
2005-12-07

Equilibrium partitioning between nonaqueous phase liquids (NAPLs) and water is a governing process for contaminants leaching from NAPLs. Conventional prediction methods, such as Raoult's law and single-parameter linear free energy relationship (SP-LFER), are inaccurate for compounds with polar functional groups. Therefore, this study introduces a polyparameter linear free energy relationship (PP-LFER) approach as a more general tool to predict NAPL-water partitioning coefficients. Our approach was evaluated using 441 experimental partitioning data from 30 references. Experimental fuel-water partitioning coefficients were generally well reproduced by existing PP-LFERs for pure solvents using either a volume-fraction weighted sum of partitioning coefficients K (linear model, R2 = 0.983, root-mean-squared error [rmse] = 0.23) or a volume-fraction weighted sum of log K (log linear model, R2 = 0.976, rmse = 0.28). Using the linear model, estimations were, in most cases, within a factor of 2 from the experimental values, regardless of the type of compounds and the presence of a fuel additive. In contrast, the log linear model considerably underestimated partitioning coefficients in the presence of strong solute-solvent hydrogen bonding. For coal tar-water partitioning coefficients (Kcoal tar/w), new PP-LFER equations were calculated based on experimental log Kcoal tar/w values of 35 compounds. The resulting regression equation was log Kcoal tar/w = 0.40(+/-0.33) + 0.34(+/-0.32)E+ 0.61(+/-0.57)S-0.55-(+/-0.61)A-5.07(+/-0.61)B + 3.22(+/-0.35)V with the rmse equal to 0.21, where E, S, A, B, and Vare Abraham's solute descriptors. Partitioning coefficients for phenol and alcohols, calculated by the above equation, were much closer to the experimental values than to those estimated by the SP-LFER approach with octanol-water partitioning coefficients. The values of the coefficients also provide insight into the properties of coal tar in terms of molecular interactions with solutes. Consequently, using the approaches presented in this study, complex organic mixture-water partitioning coefficients of a wide range of organic compounds with varying polarity can be reasonably estimated.
Iron Transport In Escherichia coli
2005-12-07

Escherichia coli is the most frequent cause of bacterial disease in the human urinary tract. E. coli strains isolated from the urine without further cultivation contain large amounts of outer membrane proteins with molecular masses of approximately 80 kDa; these proteins are transporters of Fe-siderophores and heme Under sufficient iron supply, several thousand copies of these proteins are synthesized per cell and can increase to 30,000 copies under iron-limiting growth conditions. The outer membrane transporters are the most abundant iron-transport proteins and can be detected by staining after SDS-PAGE, whereas the proteins involved in transport across the cytoplasmic membrane are made in amounts below the detection limit of protein staining and can be visualized by radiolabeling after cloning the encoding genes on multicopy plasmids. The Fesiderophores and heme transporters in the cytoplasmic membrane belong to the group of the ABC transporters, which are the most frequently occurring transport systems in bacteria. They consist of a periplasmic binding protein, one or two integral cytoplasmic membrane transport proteins, and a cytoplasmic ATPase that is associated with the inner side of the cytoplasmic membrane (Fig 1). During transport, ATP is consumed; ATP hydrolysis is initiated by binding of the substrate-loaded periplasmic protein to the inner membrane transporters. Evidence has been found that the periplasmic protein interacts with transmembrane domains and a cytoplasmically
The flux-across-surfaces theorem under conditions on the scattering state
2005-12-07

The flux-across-surfaces theorem (FAST) describes the outgoing asymptotics of\\nthe quantum flux density of a scattering state. The FAST has been proven for\\npotential scattering under conditions on the outgoing asymptote\\n (and of course under suitable conditions on the scattering\\npotential). In this article we prove the FAST under conditions on the\\nscattering state itself. In the proof we will establish also new mapping\\nproperties of the wave operators.\\n
A Novel Palladium‐Catalyzed Arylation—Dehydroaromatization Reaction: Synthesis of 7‐Aryltetralones.
2005-12-08

A new one-pot room-temperature palladium-catalyzed synthesis of 7-aryltetralones was discovered. This tandem process includes a palladium-catalyzed γ-selective arylation of the enone &lt;b&gt;4&lt;/b&gt; followed by a dehydrogenation-aromatization of the initial cross-coupling product.
Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation
2005-12-13

Cytomegalovirus (CMV) infection is a major complication after allogeneic stem cell transplantation (SCT). Valganciclovir (V-GCV) is an oral prodrug hydrolyzed to the anti-CMV drug ganciclovir (GCV). A randomized, multicenter, crossover, open-label clinical trial compared exposure to GCV after V-GCV and intravenous GCV (IV-GCV) as preemptive therapy for CMV disease in SCT. The primary objective was to compare exposure to GCV in patients with CMV infection stratified for intestinal graft-versus-host disease (I-GVHD). Secondary objectives were the assessment of safety and efficacy. Patients without I-GVHD had a higher exposure to GCV after V-GCV when compared with IV-GCV (area under the concentration-time curve from drug administration to last observed concentration after 12 hours [AUC(0-12)] 53.8 +/- 17.97 microg/mL . h [mean +/- SD] vs 39.5 +/- 13.91; P < .001; ratio of V-GCV/IV-GCV was 1.4; 90% confidence interval [CI], 1.2-1.5). This was also true in patients with I-GVHD grades I-II (AUC(0-12) 52.9 +/- 21.75 vs 33.1 +/- 12.97 mug/mL . h; P = .018; ratio 1.6; 90% CI, 1.3-2.0). Absolute bioavailability of GCV after V-GCV was approximately 75% in individuals with or without I-GVHD grades I-II. No severe GCV-related toxicity was observed and efficacy and safety was comparable (84-day follow-up). This supports the use of V-GCV in SCT, even in patients with I-GVHD grades I-II. Due to higher exposure after V-GCV compared with IV-GCV, patients should be monitored carefully for safety reasons.