julilili42/papers huggingface dataset:
Effect of Glycerol and PVA on the Conformation of Photosystem I
2011-04-15

Single-molecule spectroscopy at cryogenic temperatures was used to examine the impact of buffer solution, glycerol/buffer mixtures (25% and 66%), and poly(vinyl alcohol) (PVA) films on the conformation of photosystem I (PSI) from Thermosynechoccocus elongatus. PSI holds a number of chromophores embedded at different places within the protein complex that show distinguishable fluorescence at low temperatures. The fluorescence emission from individual complexes shows inter- and intracomplex heterogeneity depending on the solution wherein PSI was dissolved. Statistical evaluation of spectra of a large number of complexes shows that the fluorescence emission of some of these chromophores can be used as sensors for their local nanoenvironment and some as probe for the conformation of the whole protein complex. Preparation in glycerol/buffer mixtures yields a high homogeneity for all chromophores, indicating a more compact protein conformation with less structural variability. In buffer solution a distinct heterogeneity of the chromophores is observed. PSI complexes in PVA show highly heterogeneous spectra as well as a remarkable blue shift of the fluorescence emission, indicating a destabilization of the protein complex. Photosystem I prepared in PVA cannot be considered fully functional, and conclusions drawn from experiments with PSI in PVA films are of questionable value.
PKB/SGK-Resistant GSK3 Enhances Phosphaturia and Calciuria
2011-04-15

Insulin and IGF1-dependent signaling activates protein kinase B and serum and glucocorticoid inducible kinase (PKB/SGK), which together phosphorylate and inactivate glycogen synthase kinase GSK3. Because insulin and IGF1 increase renal tubular calcium and phosphorus reabsorption, we examined GSK3 regulation of phosphate transporter activity and determined whether PKB/SGK inactivates GSK3 to enhance renal phosphate and calcium transport. Overexpression of GSK3 and the phosphate transporter NaPi-IIa in Xenopus oocytes decreased electrogenic phosphate transport compared with NaPi-IIa-expressing oocytes. PKB/SGK serine phosphorylation sites in GSK3 were mutated to alanine to create gsk3(KI) mice resistant to PKB/SGK inactivation. Compared with wildtype animals, gsk3(KI) animals exhibited greater urinary phosphate and calcium clearances with higher excretion rates and lower plasma concentrations. Isolated brush border membranes from gsk3(KI) mice showed less sodium-dependent phosphate transport and Na-phosphate co-transporter expression. Parathyroid hormone, 1,25-OH vitamin D levels, and bone mineral density were decreased in gsk3(KI) mice, suggesting a global dysregulation of bone mineral metabolism. Taken together, PKB/SGK phosphorylation of GSK3 increases phosphate transporter activity and reduces renal calcium and phosphate loss.
Coordinate Regulation of Cytochrome P450 1A1 Expression in Mouse Liver by the Aryl Hydrocarbon Receptor and the β-Catenin Pathway
2011-04-16

The expression of cytochrome P450 (CYP) 1a1 and other drug-metabolizing enzymes is controlled by the aryl hydrocarbon receptor (AhR), which is activated by dioxin-type inducers leading to transcriptional induction of target genes. Here, we show that a second level of transcriptional control exists in hepatocytes, which is tightly linked to the Wnt/β-catenin/T-cell factor (TCF) signaling pathway. In transgenic mice, hepatic expression of CYP1A (and other CYP isoforms) is stimulated by the expression of mutationally activated β-catenin(S33Y) in the absence of AhR-activating compounds but repressed after knockout of β-catenin. These effects were further analyzed in vitro, and the stimulatory role of β-catenin was ascribed to a TCF-binding site within the CYP1A1 promoter. Moreover, β-catenin signaling acted cooperatively with AhR agonists via AhR-binding sites on the DNA during the induction of Cyp1a1 in vivo and in vitro. Activation of β-catenin enhanced the transactivation potential of ligand-activated AhR at its DNA-binding sites without altering the total amount of DNA-bound AhR. Coimmunoprecipitation demonstrated a physical interaction between AhR and β-catenin. Furthermore, the present results suggest that transcriptional induction of the AhR by β-catenin does not play a major role in β-catenin-dependent regulation of Cyp1a1 expression and that inhibition of β-catenin signaling by ligand-activated AhR, as recently observed in the intestine does not occur in mouse liver. In conclusion, signaling through β-catenin activates basal CYP1A1 expression and augments CYP1A1 induction by AhR ligands through enhancement of the transactivation potential of the AhR.
Evidence for mechanical and chemical alteration of iron-nickel meteorites on Mars: Process insights for Meridiani Planum
2011-04-16

The weathering of meteorites found on Mars involves chemical and physical processes that can provide clues to climate conditions at the location of their discovery. Beginning on sol 1961, the Opportunity rover encountered three large iron meteorites within a few hundred meters of each other. In order of discovery, these rocks have been assigned the unofficial names Block Island, Shelter Island, and Mackinac Island. Each rock presents a unique but complimentary set of features that increase our understanding of weathering processes at Meridiani Planum. Significant morphologic characteristics interpretable as weathering features include (1) a large pit in Block Island, lined with delicate iron protrusions suggestive of inclusion removal by corrosive interaction; (2) differentially eroded kamacite and taenite lamellae in Block Island and Shelter Island, providing relative timing through crosscutting relationships with deposition of (3) an iron oxide&amp;ndash;rich dark coating; (4) regmaglypted surfaces testifying to regions of minimal surface modification, with other regions in the same meteorites exhibiting (5) large‐scale, cavernous weathering (in Shelter Island and Mackinac Island). We conclude that the current size of the rocks is approximate to their original postfall contours. Their morphology thus likely results from a combination of atmospheric interaction and postfall weathering effects. Among our specific findings is evidence supporting (1) at least one possible episode of aqueous acidic exposure for Block Island; (2) ripple migration over portions of the meteorites; (3) a minimum of two separate episodes of wind abrasion; alternating with (4) at least one episode of coating‐forming chemical alteration, most likely at subzero temperatures.
Search for a Dark Matter Annihilation Signal from the Galactic Center Halo with H.E.S.S.
2011-04-18

A search for a very-high-energy (VHE; ≥100 GeV) γ-ray signal from self-annihilating particle dark matter (DM) is performed towards a region of projected distance r∼45-150 pc from the Galactic center. The background-subtracted γ-ray spectrum measured with the High Energy Stereoscopic System (H.E.S.S.) γ-ray instrument in the energy range between 300 GeV and 30 TeV shows no hint of a residual γ-ray flux. Assuming conventional Navarro-Frenk-White and Einasto density profiles, limits are derived on the velocity-weighted annihilation cross section (σv) as a function of the DM particle mass. These are among the best reported so far for this energy range and in particular differ only little between the chosen density profile parametrizations. In particular, for the DM particle mass of ∼1 TeV, values for (σv) above 3×10(-25) cm(3) s(-1) are excluded for the Einasto density profile.
Improved tunneling magnetoresistance at low temperature in manganite junctions grown by molecular beam epitaxy
2011-04-18

We report resistance versus magnetic field measurements for a La0.65Sr0.35MnO3/SrTiO3/La0.65Sr0.35MnO3 tunnel junction grown by molecular-beam epitaxy, that show a large field window of extremely high tunneling magnetoresistance (TMR) at low temperature. Scanning the in-plane applied field orientation through 360°, the TMR shows fourfold symmetry, i.e., biaxial anisotropy, aligned with the crystalline axis but not the junction geometrical long axis. The TMR reaches ∼1900% at 4 K, corresponding to an interfacial spin polarization of &amp;gt;95% assuming identical interfaces. These results show that uniaxial anisotropy is not necessary for large TMR, and lay the groundwork for future improvements in TMR in manganite junctions.
Small molecule dipeptidylpeptidase IV inhibitors under investigation for diabetes mellitus therapy
2011-04-18

The efficacy and safety profile of DPP IV inhibitors are promising and advantageous so far. In contrast to sulfonylureas, DPP IV inhibitors do not have an intrinsic risk for causing hypoglycemia and they are body weight neutral. Their tolerability profile is good and no specific adverse reactions have been reported. Experience so far suggests that there are no safety issues associated with inhibition of DPP IV activity by itself. Novel DPP IV inhibitors with distinct properties may offer alternative choices within this drug class.
Population density and group size effects on reproductive behavior in a simultaneous hermaphrodite
2011-04-18

We demonstrate that mating rate in C. sandrana is largely unresponsive to variation in mate availability and is maintained close to the female fitness optimum. These findings challenge the prevailing notion of male driven mating rates in simultaneous hermaphrodites and call for complementary investigations of mating rate effects on fitness through the male sexual function.
Genetic Polymorphisms as Risk Stratification Tool in Primary Preventive ICD Therapy
2011-04-18

More and more implantable cardioverter-defibrillators (ICDs) are implanted as primary prevention of sudden cardiac death (SCD). However, major problem in practice is to identify high-risk patients for SCD. Different methods for noninvasive risk stratification do not have a sufficient positive or negative predictive value. Since current approaches lead to implantation of ICDs in a large number of patients who will never suffer an arrhythmic event and simultaneously patients still die of SCD who currently did not seem eligible for primary preventive ICD implantation, there is a need for additional tools for risk stratification. Epidemiological studies point to a hereditary risk of SCD. Different susceptibility of each person concerning arrhythmogenic events might be explained by genetic polymorphisms. By obtaining an individual “pattern” of polymorphisms of genes encoding for proteins which are important in arrhythmogenesis in one patient, risk stratification in primary prevention of SCD might by improved.
Sensitivity studies for third-generation gravitational wave observatories
2011-04-19

Advanced gravitational wave detectors, currently under construction, are expected to directly observe gravitational wave signals of astrophysical origin. The Einstein Telescope (ET), a third-generation gravitational wave detector, has been proposed in order to fully open up the emerging field of gravitational wave astronomy. In this paper we describe sensitivity models for ET and investigate potential limits imposed by fundamental noise sources. A special focus is set on evaluating the frequency band below 10 Hz where a complex mixture of seismic, gravity gradient, suspension thermal and radiation pressure noise dominates. We develop the most accurate sensitivity model, referred to as ET-D, for a third-generation detector so far, including the most relevant fundamental noise contributions.
Incubation Period of Ebola Hemorrhagic Virus Subtype Zaire
2011-04-19

If the risk of new cases is to be reduced to 1% then 25 days should be used when investigating the source of an outbreak, when determining the duration of surveillance for contacts, and when declaring the end of an outbreak.
Eps8 Regulates Hair Bundle Length and Functional Maturation of Mammalian Auditory Hair Cells
2011-04-19

Hair cells of the mammalian cochlea are specialized for the dynamic coding of sound stimuli. The transduction of sound waves into electrical signals depends upon mechanosensitive hair bundles that project from the cell's apical surface. Each stereocilium within a hair bundle is composed of uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with hair bundle development and function and are known to cause deafness in mice and humans when mutated. The growth of the stereociliar actin core is dynamically regulated at the actin filament barbed ends in the stereociliary tip. We show that Eps8, a protein with actin binding, bundling, and barbed-end capping activities in other systems, is a novel component of the hair bundle. Eps8 is localized predominantly at the tip of the stereocilia and is essential for their normal elongation and function. Moreover, we have found that Eps8 knockout mice are profoundly deaf and that IHCs, but not OHCs, fail to mature into fully functional sensory receptors. We propose that Eps8 directly regulates stereocilia growth in hair cells and also plays a crucial role in the physiological maturation of mammalian cochlear IHCs. Together, our results indicate that Eps8 is critical in coordinating the development and functionality of mammalian auditory hair cells.
Evidence for a role of dystroglycan regulating the membrane architecture of astroglial endfeet
2011-04-19

Abstract The dystrophin–dystroglycan complex (DDC) is a molecular array of proteins in muscle and brain cells. The central component of the DDC is dystroglycan, which comprises α‐ and β‐subunits. α‐Dystroglycan (α‐DG) binds to extracellular matrix components such as agrin, whereas β‐dystroglycan (β‐DG) is a membrane‐spanning protein linking α‐DG to the cytoskeleton and other intracellular components such as α‐syntrophin. In astrocytes, α‐syntrophin binds to the water channel protein aquaporin‐4 (AQP4). Recently, it has been shown that AQP4 expression is unaltered in agrin‐knockout mice, but that formation of orthogonal arrays of particles (OAPs), consisting of AQP4, is abnormal. As the brain‐selective deletion of the DG gene causes a disorganization of the astroglial endfeet, we investigated whether DG deletion has an impact on AQP4. Western blotting revealed reduced AQP4 in the parenchymal but not in the superficial compartment of the astrocyte‐conditioned DG‐knockout mouse brain. Accordingly, immunohistochemical stainings of AQP4 revealed a selective loss of AQP4 in perivascular but not in superficial astroglial endfeet. In both superficial and perivascular endfeet of the DG‐knockout brain, we observed a loss of OAPs. We conclude that in the absence of DG the majority of superficial AQP4 molecules did not form OAPs, and that expression of AQP4 in perivascular endfeet is compromised. However, the decreased number of perivascular AQP4 molecules obviously did form a few OAPs, even in the absence of DG.
Magnetar oscillations in the presence of a crust
2011-04-19

We study axisymmetric perturbations of neutron star endowed with a strong\\nmagnetic field (magnetars), considering the coupled oscillations of the fluid\\ncore with the solid crust. We recover discrete oscillations based mainly in the\\ncrust and a continuum in the core. We also confirm the presence of "discrete\\nAlfv\\\\'en modes" in the gap between two contiguous continua (see Van Hooven&amp;\\nLevin (2011)) and, in addition, we can resolve some of them also inside the\\ncontinua. Our results can explain both the lower and the higher observed quasi\\nperiodical oscillations (QPOs) in SGR 1806-20 and SGR 1900+14 and put\\nconstrains on the mass, radius and crust thickness of the two magnetars.\\n
β-Lactams Interfering with PBP1 Induce Panton-Valentine Leukocidin Expression by Triggering sarA and rot Global Regulators of Staphylococcus aureus
2011-04-19

ABSTRACT Previous articles reported that beta-lactam antibiotics increase the expression of Staphylococcus aureus Panton-Valentine leukocidin (PVL) by activating its transcription. We investigated the mechanisms underlying the inductor effect of beta-lactams on PVL expression by determining targets and regulatory pathways possibly implicated in this process. We measured PVL production in the presence of oxacillin (nonselective), imipenem (penicillin-binding protein 1 [PBP1] selective), cefotaxime (PBP2 selective), cefaclore (PBP3 selective), and cefoxitin (PBP4 selective). In vitro , we observed increased PVL production consistent with luk -PV mRNA levels that were 20 to 25 times higher for community-acquired methicillin-resistant S. aureus (CA-MRSA) cultures treated with PBP1-binding oxacillin and imipenem than for cultures treated with other beta-lactams or no antibiotic at all. This effect was also observed in vivo , with increased PVL mRNA levels in lung tissues from CA-MRSA-infected mice treated with imipenem but not cefoxitin. To confirm the involvement of PBP1 inhibition in this pathway, PBP1 depletion by use of an inducible pbp1 antisense RNA showed a dose-dependent relationship between the level of pbp1 antisense RNA and the luk -PV mRNA level. Upon imipenem treatment of exponential-phase cultures, we observed an increased sarA mRNA level after 30 min of incubation followed by a decreased rot mRNA level after 1 to 4 h of incubation. Unlike the agr and saeRS positive regulators, which were nonessential for PVL induction by beta-lactams, the sarA (positive) and rot (negative) PVL regulators were necessary for PVL induction by imipenem. Our results suggest that antibiotics binding to PBP1 increase PVL expression by modulating sarA and rot , which are essential mediators of the inductor effect of beta-lactams on PVL expression.
Benchmarking improves quality in cystic fibrosis care: a pilot project involving 12 centres
2011-04-19

CF provides a model of the link between processes of health care delivery and health outcomes of patients. Quality improvement is a continuous goal in CF care with realistic potential as exemplified by our data. Accountability was introduced and transparency was improved by our pilot benchmarking project. Using the benchmarking procedure, our long-term project will reinforce standards, programmes, and individual attitudes and principles to ensure continuous quality improvement in CF health care.
Melanoma of unknown primary is correctly classified by the AJCC melanoma classification from 2009
2011-04-19

Few studies have focused on the prognosis of melanoma of unknown primary (MUP). This study aimed (i) to determine prognostic factors for patients with MUP and (ii) to investigate whether the American Joint Committee on Cancer (AJCC) 2009 classification is suitable for MUP. Among 8897 patients with melanoma attending the university department of dermatology, Tuebingen, Germany, 172 (1.9%) patients with MUP were recorded. Prognostic factors were studied using Kaplan-Meier and multivariate Cox proportional hazard models. Cutaneous and subcutaneous metastases were categorized as satellite/in-transit metastases, lymph-node metastases as regional lymph-node metastases, and all other metastases as distant metastases. Multivariate analysis found AJCC-stage at diagnosis, lactate dehydrogenase at diagnosis, number of metastases and age to be independent prognostic factors for MUP. Multivariate analyses stratified by AJCC stage showed that size of satellite/in-transit metastases (P=0.034) and number of regional lymph-node metastases (P=0.006) were significant for stage III, whereas for stage IV age (P=0.006) and lactate dehydrogenase-level at primary diagnosis (P=0.003) proved to be prognostically important. Patients with MUP can be classified according to AJCC, which presented as the strongest prognostic factor. From a management perspective it is important to notice that the majority of MUP were classified as stage III.
Molecular simulation grid
2011-04-19

MoSGrid is the acronym for Molecular Simulation Grid, a BMBF funded joint research project with the aim to offer grid services for the broad field of molecular simulations in the D-Grid infrastructure. Besides tendering various codes ranging from quantum molecular calculations (e.g. Gaussian, Turbomole) via molecular dynamics (e.g. Gromacs) to docking approaches (e.g. FlexX) for high performance computing, one of the main goals is the integration of metadata annotation for data mining and knowledge generation. Molecular simulation codes and computational resources are accessed via the MoSGrid portal (http://www.mosgrid.de), which will offer intuitive access to various tools and will support the users with workflows, for an easy import of molecular data, a simple setup and submission of calculations as well as extraction of relevant results. The portal will hide the complexity of the underlying technology by providing a unified user interface making computational chemistry in general more readily available. MoSGrid’s server-based portal is available as open-access and open-source software. Users are relieved from software installations and do not need to have knowledge about the underlying infrastructure. The portal includes portlets specifically set up for the various simulation programs. Commonly used workflows, simple or complex, can be stored in recipe repositories and are available for every user. Moreover, users can develop, improve, publish, and use workflows for their everyday tasks.
A framework and workflow system for virtual screening and molecular docking
2011-04-19

Virtual Screening and molecular docking usually require a large number of diverse and often incompatible programs.Problems arise when different programs require dissimilar file formats, are not available due to license issues, or have to be used in very different kind of ways.Furthermore, data is commonly not stored consistently and information about which tools were applied on which datasets in which way is usually lost.Thus, in practice, frequent changes between tools and environments are necessary as well asusually not losslessconversions between different formats and results obtained this way are hard to reproduce.Here we present a framework, based on the Biochemical Algorithms Library (BALL) [1], that provides a broad range of functionality, covering all common areas of interest for virtual screening and molecular docking.It includes tools for ligand/receptor preparation, interaction scoring, docking and rescoring, as well as for performing QSAR analysis and storage of molecules in a database.This framework thus greatly facilitates the application of virtual screening and docking and consistent storing and handling of data.Furthermore, all tools of our framework have been integrated into the workflow management system galaxy [2].This way, the programs can be used directly from a webbrowser, without any need for programming skills or installation of tools on the part of the user.Workflows can be easily generated, stored and reused, which makes successive application of tools much easier.All data sets and uses of tools are automatically tracked and logged, so that results obtained by use of this system are easy to reproduce.