julilili42/papers huggingface dataset:
PKG activity causes photoreceptor cell death in two retinitis pigmentosa models
2008-12-05

Abstract Photoreceptor degeneration in retinitis pigmentosa is one of the leading causes of hereditary blindness in the developed world. Although causative genetic mutations have been elucidated in many cases, the underlying neuronal degeneration mechanisms are still unknown. Here, we show that activation of cGMP‐dependent protein kinase (PKG) hallmarks photoreceptor degeneration in rd1 and rd2 human homologous mouse models. When induced in wild‐type retinae, PKG activity was both necessary and sufficient to trigger cGMP‐mediated photoreceptor cell death. Target‐specific, pharmacological inhibition of PKG activity in both rd1 and rd2 retinae strongly reduced photoreceptor cell death in organotypic retinal explants. Likewise, inhibition of PKG in vivo, using three different application paradigms, resulted in robust photoreceptor protection in the rd1 retina. These findings suggest a pivotal role for PKG activity in cGMP‐mediated photoreceptor degeneration mechanisms and highlight the importance of PKG as a novel target for the pharmacological intervention in RP.
A Pact with the Devil? Elite Alliances as Bases of Violent Religious Conflicts
2008-12-05

This article aims at explaining religious conflicts on the basis of an elite-centered theoretical model. Violent movements can only pertain on the long run if political elites organize and coordinate them centrally. The same holds true for the religious dimension of many conflicts. Religious elites have to persuade the believers of the religious nature of their struggle. Hence, in many cases religious conflicts can be traced back to alliances of religious and political elites. The first try to protect their religious communities and hope to expand their religious influence. The latter try to use religion as a resource for mobilization.
Genome Analysis of the Meat Starter Culture BacteriumStaphylococcus carnosusTM300
2008-12-06

ABSTRACT The Staphylococcus carnosus genome has the highest GC content of all sequenced staphylococcal genomes, with 34.6%, and therefore represents a species that is set apart from S. aureus , S. epidermidis , S. saprophyticus , and S. haemolyticus . With only 2.56 Mbp, the genome belongs to a family of smaller staphylococcal genomes, and the ori and ter regions are asymmetrically arranged with the replichores I (1.05 Mbp) and II (1.5 Mbp). The events leading up to this asymmetry probably occurred not that long ago in evolution, as there was not enough time to approach the natural tendency of a physical balance. Unlike the genomes of pathogenic species, the TM300 genome does not contain mobile elements such as plasmids, insertion sequences, transposons, or STAR elements; also, the number of repeat sequences is markedly decreased, suggesting a comparatively high stability of the genome. While most S. aureus genomes contain several prophages and genomic islands, the TM300 genome contains only one prophage, ΦTM300, and one genomic island, νSCA1, which is characterized by a mosaic structure mainly composed of species-specific genes. Most of the metabolic core pathways are present in the genome. Some open reading frames are truncated, which reflects the nutrient-rich environment of the meat starter culture, making some functions dispensable. The genome is well equipped with all functions necessary for the starter culture, such as nitrate/nitrite reduction, various sugar degradation pathways, two catalases, and nine osmoprotection systems. The genome lacks most of the toxins typical of S. aureus as well as genes involved in biofilm formation, underscoring the nonpathogenic status.
Snail phenotypic variation and stress proteins: do different heat response strategies contribute to Waddington's widget in field populations?
2008-12-08

Abstract On the basis of studies with laboratory strains of Drosophila and Arabidopsis , it has been hypothesized that potential buffers to the expression of phenotypic morphological variation, such as Hsp90 and possibly Hsp70, represent important components of Waddington's widget, which may confer capacitive evolution. As studies on field populations of living organisms to test this hypothesis are lacking, we tested whether a heat response strategy involving high stress protein levels is associated with low morphological variation and vice versa, using four natural populations of Mediterranean pulmonate snails. In response to 8 hr of elevated temperatures, a population of Xeropicta derbentina with uniform shell pigmentation pattern showed remarkably high Hsp70 but low Hsp90 levels. In contrast, a highly variable population of Cernuella virgata kept both Hsp90 and Hsp70 levels low when held at diverse though environmentally relevant temperatures. Two other populations ( Theba pisana and another X. derbentina population) with intermediate variation in shell pigmentation pattern were also intermediate in inducing Hsp70, though Hsp90 was maintained at a low level. The observed correlation of stress protein levels and coloration pattern variation provide the first indirect evidence for an association of stress proteins with Waddington's widget under natural conditions. J. Exp. Zool. (Mol. Dev. Evol.) 312B:136–147, 2009 . © 2008 Wiley‐Liss, Inc.
Neuronal plasticity of the haptic system
2008-12-08

To survive in a continuously changing environment either as individual or species, organisms need to adapt. Since environmental changes occur on different time scales ranging from milliseconds to hundreds of centuries, nature provides an arsenal of different mechanisms and strategies of adaptation. Immediate adaptations are necessary in life-threatening situations. Alternatively, changes in climate, food availability, and the appearance of competitors and predators alter an individual's behaviour, and might, on a longer timescale, even shape organisms across generations. Adaptation of the latter type occurs mainly on an evolutionary basis, which acts on genetic information. In contrast, adaptation referring to changes in individual's behaviour is realised by learning which is mediated on a neuronal level.
Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1
2008-12-09

Novel mesenchymal stem cells subsets with distinct phenotypic and functional properties were identified. Our data suggest that the MSCA-1(+)CD56(+) subset is an attractive starting population for autologous chondrocyte transplantation.
ERK-mediated regulation of leukotriene biosynthesis by androgens: A molecular basis for gender differences in inflammation and asthma
2008-12-09

5-Lipoxygenase initiates the biosynthesis of leukotrienes, lipid mediators involved in normal host defense and in inflammatory and allergic disorders. Despite an obvious gender bias in leukotriene-related diseases (e.g., asthma), gender aspects have been neglected in studies on leukotrienes and 5-lipoxygenase. Here, we show that leukotriene formation in stimulated whole blood or neutrophils from males is substantially lower compared with females, accompanied by changed 5-lipoxygenase trafficking. This is due to gender-specific differential activation of extracellular signal-regulated kinases (ERKs). The differences are directly related to variant male/female testosterone plus 5α-dihydrotestosterone levels, and addition of 5α-dihydrotestosterone to female blood or neutrophils reduced the high (female) LT biosynthesis capacity to low (male) levels. In conclusion, regulation of ERKs and leukotriene formation by androgens constitutes a molecular basis for gender differences in the inflammatory response, and in inflammatory diseases such as asthma.
NONRESUSCITATED ENDOTOXEMIA INDUCES MICROCIRCULATORY HYPOXIC AREAS IN THE RENAL CORTEX IN THE RAT
2008-12-09

The pathophysiology of acute renal failure (ARF) in sepsis is only partly understood. In several animal models of septic ARF, no profound tissue hypoxia or decrease in microcirculatory PO2 (microPO2) can be seen. We hypothesized that heterogeneity of microcirculatory oxygen supply to demand in the kidney is obscured when looking at the average microPO2 during endotoxemia. In 20 anesthetized and ventilated rats, MAP, renal blood flow (RBF), and creatinine clearance (CLcrea) were recorded. Renal microPO2 was measured by phosphorescence quenching, allowing measurement of microPO2 distributions. Five animals received a 1-h LPS infusion (10 mg kg h). In 5 rats, RBF was mechanically reduced to 2.1 +/- 0.2 mL min. Five animals served as time control. LPS infusion significantly reduced RBF to 2.1 +/- 0.2 mL min and induced anuria. Average cortical microPO2 decreased from 68 +/- 4 to 52 +/- 6 mmHg, with a significant left shift in the cortical oxygen histogram toward hypoxia. This shift could not be observed in animals receiving mechanical RBF reduction. In these animals, CLcrea was reduced to 50%. An additional group of rats (n = 5) received fluid resuscitation. In these animals, RBF was restored to baseline, CLcrea increased approximately 50%, and the cortical microcirculatory hypoxic areas disappeared after resuscitation. In conclusion, endotoxemia was associated with the occurrence of cortical microcirculatory hypoxic areas that are not detected in the average PO2 measurement, proving the hypothesis of our study. These observations suggest the involvement of hypoxia in the pathogenesis of endotoxemia-induced ARF.
Semifluxon Molecule under Control
2008-12-09

Josephson junctions with a phase drop of pi in the ground state allow us to create vortices of supercurrent carrying only half of the magnetic flux quantum Phi0 approximately 2.07 x 10(-15) Wb. Such semifluxons have twofold degenerate ground states denoted upward arrow (with flux +Phi0/2 and supercurrent circulating clockwise) and downward arrow (with flux -Phi0/2 and supercurrent circulating counterclockwise). We investigate a molecule consisting of two coupled semifluxons in a 0-pi-0 long Josephson junction. The fluxes (polarities) of semifluxons are measured by two on-chip SQUIDs. By varying the dc bias current applied to the 0-pi-0 junction, we demonstrate controllable manipulation and switching between two states, upward arrow downward arrow and downward arrow upward arrow, of a semifluxon molecule. These results provide a major step towards employing semifluxons as bits or qubits for classical and quantum digital electronics.
DFT studies of the σ-donor/π-acceptor properties of [SnCB10H11]– and its relationship to [SnCl3]–, CO, PF3, [SnB11H11]2–, SnC2B9H11, and related SnC2BnHn+2 compounds
2008-12-09

The 1,2-carbastanna-closo-dodecaborate, [SnCB 10 H 11 ] – , was found via DFT calculations to have intermediate σ-donor/π-acceptor properties between those of [SnB 11 H 11 ] 2– and 3,1,2-SnC 2 B 9 H 11 , and quite similar HOMO and LUMO energies and shapes to those of [SnCl 3 ] – , which is a stronger σ-donor and weaker π-acceptor than CO or PF 3 . The non-carbon containing cluster [SnB 11 H 11 ] 2– is shown to be a very strong donor, whereas the dicarbon cluster 3,1,2-SnC 2 B 9 H 11 is a poor σ-donor but good Lewis acid, consistent with experimental results. Thus, these systems can be tuned across a very wide range via isolobal replacement of [BH] – for CH vertices. The higher negative charge in the non-carbon-containing systems, as well as the fact that boron is more electropositive than carbon, contribute to the increased energies of both HOMO and LUMO in the stannaboranes compared to the stannacarboranes, explaining their relative donor and acceptor properties.Key words: DFT calculations, tin, borane cluster.
Surreptitious hyperkalaemia and its complications
2008-12-09

Surreptitious hyperkalaemia is not a common problem, particularly in patients not yet dialysis dependent. We encountered a patient who baffled her physicians and their consultants, who nonetheless proposed life-saving treatments and novel explanations. However, according to the maxim that common things are common and rare things are rare, we solved the problem by focusing on the accompanying anion.
BK channels in innate immune functions of neutrophils and macrophages
2008-12-10

Abstract Oxygen-dependent antimicrobial activity of human polymorphonuclear leukocytes (PMNs) relies on the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate oxidants. As the oxidase transfers electrons from NADPH the membrane will depolarize and concomitantly terminate oxidase activity, unless there is charge translocation to compensate. Most experimental data implicate proton channels as the effectors of this charge compensation, although large-conductance Ca2+-activated K+ (BK) channels have been suggested to be essential for normal PMN antimicrobial activity. To test this latter notion, we directly assessed the role of BK channels in phagocyte function, including the NADPH oxidase. PMNs genetically lacking BK channels (BK−/−) had normal intracellular and extracellular NADPH oxidase activity in response to both receptor-independent and phagocytic challenges. Furthermore, NADPH oxidase activity of human PMNs and macrophages was normal after treatment with BK channel inhibitors. Although BK channel inhibitors suppressed endotoxin-mediated tumor necrosis factor-α secretion by bone marrow-derived macrophages (BMDMs), BMDMs of BK−/− and wild-type mice responded identically and exhibited the same ERK, PI3K/Akt, and nuclear factor-κB activation. Based on these data, we conclude that the BK channel is not required for NADPH oxidase activity in PMNs or macrophages or for endotoxin-triggered tumor necrosis factor-α release and signal transduction BMDMs.
Description ofNeoliodes dominicusn. sp. (Acari, Oribatida) from dominican amber, aided by synchrotron x-ray microtomography
2008-12-10

The nearly ubiquitous mite suborder Oribatida, which comprises mostly mycophages and saprophages in organic soil horizons, has a long geological history. Early derivative taxa are known from middle and late Devonian deposits (Norton et al., 1988; Subías and Arillo, 2002) and members of the highly derived cohort Brachypylina have existed since the Jurassic (Krivolutsky and Krasilov, 1977, Selden et al., 2008). The group is commonly represented as inclusion-fossils in amber, with about 100 species known worldwide. Except for four Cretaceous fossils from Siberia (Bulanova-Zachvatkina, 1974; Krivolutsky and Ryabinin, 1976) and Spain (Arillo and Subías, 2000, 2002), the named amber species are of Tertiary age. The majority of these have been discovered in the Priabonian (middle Eocene) Baltic amber deposits of northern Europe (Labandeira et al., 1997; Norton, 2006).
Percutaneous closure of a periprosthetic leakage after mitral valve reoperation due to recurrent endocarditis
2008-12-10

Abstract Paravalvular leakage following the atrioventricular valve replacement, though mostly harmless with insignificant morbidity, can result in heart failure and significant hemolysis that requires treatment. Reoperation is still the treatment of choice, but there is a high risk of recurrence, especially in patients with a history of endocarditis and/or those who have already undergone reoperation for paravalvular leakage. Recently, percutaneous closure of perivalvular leaks with occluders or coils have become an alternative to surgery. However, up to now, the collective of patients who benefit from this approach still has to be defined. Here, we present a case of a highly symptomatic 64‐year‐old male with severe hemolysis caused by paravalvular leakages after reoperation of a mechanical mitral valve replacement due to recurrent endocarditis. © 2009 Wiley‐Liss, Inc.
Clothfighters
2008-12-10

"Clothfighters" was produced by students of audio-visual media at the Stuttgart Media University (HdM), in cooperation with the WSI-GRIS, Universität Tübingen. The idea of this short animation was to work with and test an Autodesk Maya plug-in for cloth simulation developed at the GRIS. The shape of the characters should only be defined by the clothes they were wearing; the actual geometries of their bodies were to be invisible.
High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease
2008-12-11

Cardiorespiratory fitness, independently of total adiposity, body fat distribution and exercise intensity, determines liver fat content in humans, suggesting that fitness and liver fat are causally related to each other. Moreover, measurement of fitness at baseline predicts the effectiveness of a lifestyle intervention in reducing hepatic steatosis in patients with NAFLD.
Structure of Reovirus σ1 in Complex with Its Receptor Junctional Adhesion Molecule-A
2008-12-11

Viral attachment to specific host receptors is the first step in viral infection and serves an essential function in the selection of target cells. Mammalian reoviruses are highly useful experimental models for studies of viral pathogenesis and show promise as vectors for oncolytics and vaccines. Reoviruses engage cells by binding to carbohydrates and the immunoglobulin superfamily member, junctional adhesion molecule-A (JAM-A). JAM-A exists at the cell surface as a homodimer formed by extensive contacts between its N-terminal immunoglobulin-like domains. We report the crystal structure of reovirus attachment protein sigma1 in complex with a soluble form of JAM-A. The sigma1 protein disrupts the JAM-A dimer, engaging a single JAM-A molecule via virtually the same interface that is used for JAM-A homodimerization. Thus, reovirus takes advantage of the adhesive nature of an immunoglobulin-superfamily receptor by usurping the ligand-binding site of this molecule to attach to the cell surface. The dissociation constant (K(D)) of the interaction between sigma1 and JAM-A is 1,000-fold lower than that of the homophilic interaction between JAM-A molecules, indicating that JAM-A strongly prefers sigma1 as a ligand. Analysis of reovirus mutants engineered by plasmid-based reverse genetics revealed residues in sigma1 required for binding to JAM-A and infectivity of cultured cells. These studies define biophysical mechanisms of reovirus cell attachment and provide a platform for manipulating reovirus tropism to enhance vector targeting.
Characterization of Sorbent Properties of Soil Organic Matter and Carbonaceous Geosorbents Using n-Alkanes and Cycloalkanes as Molecular Probes
2008-12-11

Nonspecific interactions and modes (i.e., adsorption vs absorption) of sorption by noncondensed, amorphous organic phases (here termed organic matter; OM) in soils and by rigid, aromatic, and condensed phases (termed carbonaceous geosorbents; CGs) were investigated using n-alkanes and cycloalkanes as molecular probes. Sorption isotherms of n- and cyclooctane from water for seven CGs (charcoal, lignite coke, activated carbon, graphite, partially oxidized graphite, diesel soot, bituminous coal), four sorbents with a predominance of OM (lignite, peat, two sapric soils), and two soils containing OM and high amounts of CGs were measured in batch systems. The peat and the sapric soils showed extensively linear sorption, while the CGs exhibited highly nonlinear (Freundlich exponents 0.2-0.7) and strong (Koc values being up to 10(5) times those for the OM-rich materials at low concentrations) sorption for the alkanes studied, showing that enhanced sorption by CGs can occur to completely apolar sorbates that do not undergo any specific interaction. Sorption by CGs was generally stronger and more nonlinear for n-octane than for cyclooctane, which suggests a strong dependence of sorption on the 3-D structure of sorbate molecules. The n-octane-to-cyclooctane sorption coefficient ratios (Kn/Kc) for adsorption to CGs were > or = 1, being distinctly different from those for absorption to the OM-rich materials (Kn/Kc < 1). The measured sorption isotherms and the CG compositions in the soils determined by quantitative petrography analysis suggest, however, that CGs occurring in soils may be far less effective sorbents than the reference CGs used in the sorption experiments at least for nonspecifically interacting sorbates, probably because of competitive sorption and/or pore blocking by natural OM. The presented approaches and results offer a basis for interpreting sorption data for other organic compounds, as nonspecific interactions and sorption modes are relevant for any compound.
Preparation of Some Glycosyl Amino Acid Building Blocks via Click Reaction and Construction of a Glycotetrapeptide Library Using Spot Synthesis
2008-12-11

The copper-catalyzed 1,3-dipolar cycloaddition reaction between ethyl 2,3,4-tri-O-actetyl-6-azido-6-deoxy-1-thio-β -d-glucopyranoside (2), ethyl 2,3,4-tri-O-actetyl-6-azido-6-deoxy-1-thio-β -d-galactopyranoside (4), methyl 2,3,4-tri-O-acetyl-6-azido-6-deoxy-α -d-mannopyranoside (7), and methyl 2,3,6-tri-O-acetyl-2-azido-2-deoxy-β -d-glucopyranoside (9), and tert-butyl-protected Fmoc-asparaginic acid propargylamide (10) gave the corresponding protected glycosyl amino acid building blocks 11, 13, 15, and 17 in 67% to 95% yield. The latter were converted into the corresponding pentafluorophenyl esters 12, 14, 16, and 18, which were used for a spot synthesis of a combinatorial library containing 256 glycotetrapeptides. The library was screened for lectin-binding affinity with the lectins Concanavalin A (Con A), phaseolus vulgaris (PHA-E), and galantus nivalis (GNA).
Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus
2008-12-12

Monocytes play a major role in the cellular defence against Aspergillus fumigatus in immunocompromised patients. To obtain a better understanding of the mechanisms involved in this interaction, phagocytosis and gene expression profiling of human monocytes was carried out after incubation with A. fumigatus resting, swollen and germinating conidia and hyphae (for 3, 6 and 9 h). The majority of monocytes phagocytosed up to three conidia during the first 3 h of incubation. Microarray analysis showed an increased expression level of immune-relevant genes, which was dependent on the germination state of the fungus and the incubation period. Among these genes, those encoding interleukin-8, macrophage inflammatory protein 3- α (CCL20) and monocyte chemotactic protein-1 (CCL2) were found to be potential key regulators involved in the A. fumigatus -induced immune response. In addition, A. fumigatus was found to be an inducer of the genes encoding urokinase type plasminogen activator (uPA), urokinase type plasminogen activator receptor (uPAR),plasminogen activator inhibitor (PAI), pentraxin-3 (PTX3) and intercellular adhesion molecule-1 (ICAM-1), which, in combination, may contribute to thrombosis and local lung tissue injury.