julilili42/papers huggingface dataset:
S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway
2008-03-13

Abstract The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity against various cells, especially tumor cells. Here, we present evidence that S100A8/A9 also has cell growth-promoting activity at low concentrations. Receptor of advanced glycation end product (RAGE) gene silencing and cotreatment with a RAGE-specific blocking antibody revealed that this activity was mediated via RAGE ligation. To investigate the signaling pathways, MAPK phosphorylation and NF-κB activation were characterized in S100A8/A9-treated cells. S100A8/A9 caused a significant increase in p38 MAPK and p44/42 kinase phosphorylation, and the status of stress-activated protein kinase/JNK phosphorylation remained unchanged. Treatment of cells with S100A8/A9 also enhanced NF-κB activation. RAGE small interfering RNA pretreatment abrogated the S100A8/A9-induced NF-κB activation. Our data indicate that S100A8/A9-promoted cell growth occurs through RAGE signaling and activation of NF-κB.
Auxin transport inhibitors impair vesicle motility and actin cytoskeleton dynamics in diverse eukaryotes
2008-03-13

Many aspects of plant development, including patterning and tropisms, are largely dependent on the asymmetric distribution of the plant signaling molecule auxin. Auxin transport inhibitors (ATIs), which interfere with directional auxin transport, have been essential tools in formulating this concept. However, despite the use of ATIs in plant research for many decades, the mechanism of ATI action has remained largely elusive. Using real-time live-cell microscopy, we show here that prominent ATIs such as 2,3,5-triiodobenzoic acid (TIBA) and 2-(1-pyrenoyl) benzoic acid (PBA) inhibit vesicle trafficking in plant, yeast, and mammalian cells. Effects on micropinocytosis, rab5-labeled endosomal motility at the periphery of HeLa cells and on fibroblast mobility indicate that ATIs influence actin cytoskeleton. Visualization of actin cytoskeleton dynamics in plants, yeast, and mammalian cells show that ATIs stabilize actin. Conversely, stabilizing actin by chemical or genetic means interferes with endocytosis, vesicle motility, auxin transport, and plant development, including auxin transport-dependent processes. Our results show that a class of ATIs act as actin stabilizers and advocate that actin-dependent trafficking of auxin transport components participates in the mechanism of auxin transport. These studies also provide an example of how the common eukaryotic process of actin-based vesicle motility can fulfill a plant-specific physiological role.
Self/nonself perception and recognition mechanisms in plants: a comparison of self‐incompatibility and innate immunity
2008-03-13

Summary Analyses of emerging concepts indicate that parallels exist between self‐incompatibility and pathogen recognition. In the case of surveillance of ‘nonself’, plant immune responses are triggered either by pattern recognition receptors (PRRs) that detect conserved pathogen‐associated molecular patterns (PAMPs) or by resistance (R) proteins recognizing isolate‐specific pathogen effectors. PAMP detection is an important component of innate immunity in plants and serves as an early warning system for the presence of potential pathogens and activation of plant defense mechanisms. In the Brassicaceae, the recognition of ‘self’ and self‐incompatibility are components of a receptor‐ligand based mechanism that utilizes an S receptor kinase (SRK) to perceive and reject ‘self’‐pollen. SRK is an S‐domain receptor‐like kinase (RLK), which in turn is part of the RLK family, some members of which represent PRRs involved in the detection of PAMPs. S‐domain RLKs also occur in species that do not exhibit self‐incompatibility and are up‐regulated in response to wounding, PAMPs and pathogen recognition. Although evolution may have driven expansion of certain RLK families to serve roles in particular physiological processes, this may not exclude these receptor types from functioning in different programs. Recent findings on self/nonself recognition are reviewed and conceptual and mechanistic links between microbial recognition and self‐incompatibility are discussed.
Calibrating Differential Interference Contrast Microscopy with dual-focus Fluorescence Correlation Spectroscopy
2008-03-14

We present a novel calibration technique for determining the shear distance of a Nomarski Differential Interference Contrast prism, which is used in Differential Interference Contrast microscopy as well as for the recently developed dual-focus fluorescence correlation spectroscopy. In both applications, an exact knowledge of the shear distance induced by the Nomarski prism is important for a quantitative data evaluation. In Differential Interference Contrast microscopy, the shear distance determines the spatial resolution of imaging, in dual-focus fluorescence correlation spectroscopy, it represents the extrinsic length scale for determining diffusion coefficients. The presented calibration technique is itself based on a combination of fluorescence correlation spectroscopy and dynamic light scattering. The method is easy to implement and allows for determining the shear distance with nanometer accuracy.
The Virulence Regulator Sae ofStaphylococcus aureus:Promoter Activities and Response to Phagocytosis-Related Signals
2008-03-15

ABSTRACT The two-component system SaeRS of Staphylococcus aureus is closely involved in the regulation of major virulence factors. However, little is known about the signals leading to saeRS activation. A total of four overlapping transcripts (T1 to T4) from three different transcription starting points are expressed in the sae operon. We used a β-galactosidase reporter assay to characterize the putative promoter regions within the saeRS upstream region. The main transcript T2 is probably generated by endoribonucleolytic processing of the T1 transcript. Only two distinct promoter elements (P1 and P3) could be detected within the saeRS upstream region. The P3 promoter, upstream of saeRS , generates the T3 transcript, includes a cis -acting enhancer element and is repressed by saeRS . The most distal P1 promoter is strongly autoregulated, activated by agr , and repressed by sigma factor B. In strain Newman a mutation within the histidine kinase SaeS leads to a constitutively activated sae system. Evaluation of different external signals revealed that the P1 promoter in strain ISP479R and strain UAMS-1 is inhibited by low pH and high NaCl concentrations but activated by hydrogen peroxide. The most prominent induction of P1 was observed at subinhibitory concentrations of α-defensins in various S. aureus strains, with the exception of strain ISP479R and strain COL. P1 was not activated by the antimicrobial peptides LL37 and daptomycin. In summary, the results indicate that the sensor molecule SaeS is activated by alteration within the membrane allowing the pathogen to react to phagocytosis related effector molecules.
Proximicins A, B, and C—Antitumor Furan Analogues of Netropsin from the Marine Actinomycete Verrucosispora Induce Upregulation of p53 and the Cyclin Kinase Inhibitor p21
2008-03-17

Drugs from the sea: Three new netropsin-type antibiotics (1–3) with a hitherto unknown furan core structure have been isolated from marine actinomycete strains and their structures elucidated by means of mass spectrometry and 2D NMR spectroscopy. The compounds show antitumor activity and, in contrast to netropsin, they induce upregulation of p53 and the cyclin kinase inhibitor p21. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705295_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Anorexia nervosa: Selective processing of food‐related word and pictorial stimuli in recognition and free recall tests
2008-03-17

Abstract Objective: Maladaptive processing of food cues is considered pivotal in the psychopathology of anorexia nervosa. However, the influence of hunger and differences in processing because of the type of stimuli remain largely unclear. Method: Memory bias for food‐related pictorial and semantic stimuli was assessed in a recognition and a free recall test in 16 anorexia nervosa (AN) patients, 16 control participants with food intake prior to the study (CG‐FI) and 16 control participants with a fasting period prior to the study (CG‐NF). Results: Compared with CG‐FI participants, both AN and CG‐NF participants responded faster to food‐related as compared with neutral words ( p &lt; .001) in the recognition test. Differences were found for word but not for pictorial stimuli. No group differences were observed with respect to the number of correct retrievals in either the recognition or the free recall test. Conclusion: The present study found behavioral indications of abnormal processing of food‐related and neutral stimuli in anorectic patients similar to those found in fasted healthy controls. Results are discussed in terms of self‐schemata in eating disorders, competitive interference, and levels of processing. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008
Mutation of the PDK1 PH Domain Inhibits Protein Kinase B/Akt, Leading to Small Size and Insulin Resistance
2008-03-18

PDK1 activates a group of kinases, including protein kinase B (PKB)/Akt, p70 ribosomal S6 kinase (S6K), and serum and glucocorticoid-induced protein kinase (SGK), that mediate many of the effects of insulin as well as other agonists. PDK1 interacts with phosphoinositides through a pleckstrin homology (PH) domain. To study the role of this interaction, we generated knock-in mice expressing a mutant of PDK1 incapable of binding phosphoinositides. The knock-in mice are significantly small, insulin resistant, and hyperinsulinemic. Activation of PKB is markedly reduced in knock-in mice as a result of lower phosphorylation of PKB at Thr308, the residue phosphorylated by PDK1. This results in the inhibition of the downstream mTOR complex 1 and S6K1 signaling pathways. In contrast, activation of SGK1 or p90 ribosomal S6 kinase or stimulation of S6K1 induced by feeding is unaffected by the PDK1 PH domain mutation. These observations establish the importance of the PDK1-phosphoinositide interaction in enabling PKB to be efficiently activated with an animal model. Our findings reveal how reduced activation of PKB isoforms impinges on downstream signaling pathways, causing diminution of size as well as insulin resistance.
Biological Activities of Novel Gyrase Inhibitors of the Aminocoumarin Class
2008-03-18

ABSTRACT Thirty-one aminocoumarin antibiotics derived from mutasynthesis experiments were investigated for their biological activities. Their inhibitory activities toward Escherichia coli DNA gyrase were determined in two different in vitro assays: an ATPase assay and a DNA supercoiling assay. The assays gave a similar rank order of the activities of the compounds tested, although the absolute 50% inhibitory concentrations (IC 50 s) obtained in each assay were different. To confirm that the compounds also acted as gyrase inhibitors in vivo, reporter gene assays were carried out with E. coli by using gyrA and sulA promoter fusions with the luxCDABE operon. A strong induction of both promoters was observed for those compounds that showed gyrase inhibitory activity in the biochemical assays. Compounds carrying analogs of the prenylated benzoyl moiety (ring A) of clorobiocin that were structurally very different showed high levels of activity both in the biochemical assay and in the reporter gene assay, indicating that the structure of this moiety can be varied considerably without a loss of affinity for bacterial gyrase. The experimentally determined IC 50 s were compared to the binding energies calculated in silico, which indicated that a shift of the pyrrole carboxylic acid moiety from the O-3′′ to the O-2′′ position of the deoxysugar moiety has a significant impact on the binding mode of the compounds. The aminocoumarin compounds were also investigated for their MICs against different bacterial pathogens. Several compounds showed high levels of activity against staphylococci, including a methicillin-resistant Staphylococcus aureus strain. However, they showed only poor activities against gram-negative strains.
Anchor Side Chains of Short Peptide Fragments Trigger Ligand-Exchange of Class II MHC Molecules
2008-03-18

Class II MHC molecules display peptides on the cell surface for the surveillance by CD4+ T cells. To ensure that these ligands accurately reflect the content of the intracellular MHC loading compartment, a complex processing pathway has evolved that delivers only stable peptide/MHC complexes to the surface. As additional safeguard, MHC molecules quickly acquire a ‘non-receptive’ state once they have lost their ligand. Here we show now that amino acid side chains of short peptides can bypass these safety mechanisms by triggering the reversible ligand-exchange. The catalytic activity of dipeptides such as Tyr-Arg was stereo-specific and could be enhanced by modifications addressing the conserved H-bond network near the P1 pocket of the MHC molecule. It affected both antigen-loading and ligand-release and strictly correlated with reported anchor preferences of P1, the specific target site for the catalytic side chain of the dipeptide. The effect was evident also in CD4+ T cell assays, where the allele-selective influence of the dipeptides translated into increased sensitivities of the antigen-specific immune response. Molecular dynamic calculations support the hypothesis that occupation of P1 prevents the ‘closure’ of the empty peptide binding site into the non-receptive state. During antigen-processing and -presentation P1 may therefore function as important “sensor” for peptide-load. While it regulates maturation and trafficking of the complex, on the cell surface, short protein fragments present in blood or lymph could utilize this mechanism to alter the ligand composition on antigen presenting cells in a catalytic way.
Oligophenylenevinylenes in Spatially Confined Nanochannels: Monitoring Intermolecular Interactions by UV/Vis and Raman Spectroscopy
2008-03-18

Abstract Perhydrotriphenylene‐based channel‐forming inclusion compounds (ICs) and thin films made of polyphenylenevinylene (PPV)‐type oligomers with terminal alkoxy groups are investigated and compared in a combined experimental and theoretical approach. Interchromophore interactions and host‐guest interactions are elucidated by UV/Vis and Raman spectroscopy. The impact of the local environment of the chromophore on the optical and photophysical properties is discussed in light of quantum‐chemical calculations. In stark contrast to thin films where preferential side‐by‐side orientation leads to quenching of photoluminescence (PL) via non‐emissive traps, the ICs are found to be attractive materials for opto‐electronic applications: they offer high chromophore concentrations, but at the same time behave as quasi‐isolated entities of tightly packed, well‐oriented objects with high PL quantum yields and the possibility of color tuning.
Non-tuberculous mycobacterial infection of the parotid gland in an immunosuppressed adult
2008-03-18

Infections of the parotid gland with non-tuberculous mycobacteria (NTM) are rarely described. Here, we report on an infection of the parotid gland caused by Mycobacterium avium and give a literature-based overview about this entity. In the light of a global increase of mycobacterial infections, unusual manifestations have to be considered and should be included in the differential diagnosis when dealing with solid lesions of uncertain aetiology in the head and neck region.
The Proximity-Concentration Trade-Off under Goods Price and Exchange Rate Uncertainty
2008-03-18

The underlying model combines the proximity-concentration trade-off framework with the real option approach. In contrast to the latest trade models, uncertainty is introduced as a continuous phenomenon. Furthermore, the model contains the innovation of comparing two option values simultaneously. The implementation of goods price uncertainty turns out to reduce the probability of entering a new market as an exporter. FDI becomes the optimal entry mode with increasing uncertainty. Additionally, the model is extended by implementing exchange rate uncertainty in a period of appreciation
Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis
2008-03-19

Here, we show that CDK2, an S-phase cyclin-dependent kinase, is a novel target for Akt during cell cycle progression and apoptosis. Akt phosphorylates CDK2 at threonine 39 residue both in vitro and in vivo. Although CDK2 threonine 39 phosphorylation mediated by Akt enhances cyclin-A binding, it is dispensable for its basal binding and the kinase activity. In addition, for the first time, we report a transient nucleo-cytoplasmic shuttling of Akt during specific stages of the cell cycle, in particular during the late S and G2 phases. The Akt that is re-localized to the nucleus phosphorylates CDK2 and causes the temporary cytoplasmic localization of the CDK2–cyclin-A complex. The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Thus, the constitutive activation of the Akt/CDK2 pathway and changed subcellular localization promotes apoptosis. By contrast, the transient, physiological Akt/CDK2 activation is necessary for cell cycle progression.
Influence of an inner disc on the orbital evolution of massive planets migrating in resonance
2008-03-19

Context: The formation of resonant planet pairs in exoplanetary systems involves planetary migration inside the protoplanetary disc. After a resonant capture, subsequent migration leads to a large increase in planetary eccentricities, if no damping mechanism is applied. This has led to the conclusion that the migration of resonant planetary systems cannot take place across large radial distances, but must be terminated rapidly by disc dissipation. &lt;BR /&gt;Aims: We investigate if the presence of an inner disc could supply eccentricity damping to the inner planet, and if this effect could explain observed eccentricities in some planetary systems. &lt;BR /&gt;Methods: We compute hydrodynamic simulations of giant planets, in orbits of a given eccentricity about an inner gas disc, and measure the effect of the gas disc on the planetary orbital parameters. We perform detailed long-term calculations of the GJ 876 system. We complete N-body simulations, which include artificial forces on the planets that recreate the effect of the inner and outer discs. &lt;BR /&gt;Results: We find that we cannot neglect the influence of the inner disc, and that the disc could explain the observed eccentricities. In particular, we reproduce the orbital parameters of a few systems engaged in 2:1 mean motion resonances: GJ 876, HD 73 526, HD 82 943, and HD 128 311. Analytically, we derive the effect that the inner disc should have on the inner planet to reach a specific orbital configuration, for any given damping effect of the outer disc on the outer planet. &lt;BR /&gt;Conclusions: We conclude that an inner disc, even though difficult to model properly in hydrodynamical simulations, should be taken into account because of its damping effect on the eccentricity of the inner planet. By including this effect, we can explain quite naturally the observed orbital elements of the pairs of known resonant exoplanets.
COINS, ARTEFACTS AND ISOTOPES—ARCHAEOMETALLURGY ANDARCHAEOMETRY*
2008-03-19

Archaeometallurgy is one of the earliest manifestations of archaeometric research, using science‐based approaches to address cultural–historical questions. This review first outlines the extent of the field, defining in some detail the main branches of archaeometallurgy, and their specific methodological approaches. It then looks at some of the early publications pioneering archaeometallurgical research, to set the scene for the publication pattern of archaeometallurgy in general, and the role that Archaeometry played in publishing archaeometallurgical research. The analysis of archaeometallurgy‐themed publications in Archaeometry , their change over time and their relationship to the total range of work done in the field indicates that there is a rather narrowly defined and specific type of archaeometallurgy that gets published in Archaeometry , initially with a strong focus on coin and object analysis, often combined with method developments. The more recent developments in isotope‐based studies in archaeometallurgy find only a limited representation in the journal, despite the leading role that the Isotrace Laboratory played in this discipline, for some considerable length of time. More recently, this Archaeometry ‐specific ‘flavour’ of archaeometallurgy seems to weaken, with an increase of papers on iron and on primary production in general, subjects still much under‐represented.
Exploring a SNR/molecular cloud association within HESS J1745–303
2008-03-19

Aims. HESS J1745−303 is an extended, unidentified VHE (very high energy) gamma-ray source discovered using HESS in the Galactic Plane&#13;\\nSurvey. Since no obvious counterpart has previously been found in longer-wavelength data, the processes that power the VHE emission are not&#13;\\nwell understood.&#13;\\nMethods. Combining the latest VHE data with recent XMM-Newton observations and a variety of source catalogs and lower-energy survey data,&#13;\\nwe attempt to match (from an energetic and positional standpoint) the various parts of the emission of HESS J1745−303 with possible candidates.&#13;\\nResults. Though no single counterpart is found to fully explain the VHE emission, we postulate that at least a fraction of the VHE source may be&#13;\\nexplained by a supernova-remnant/molecular-cloud association and/or a high-spin-down-flux pulsar