julilili42/papers huggingface dataset:
Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1
2009-08-01

Abstract Prostaglandin E2 (PGE2) plays a crucial role in the apparent link between tumor growth and chronic inflammation. Cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1, which are overexpressed in many cancers, are functionally coupled and thus produce massive PGE2 in various tumors. Curcumin, a polyphenolic β-diketone from tumeric with anti-carcinogenic and anti-inflammatory activities, was shown to suppress PGE2 formation and to block the expression of COX-2 and of microsomal PGE2 synthase-1. Here, we identified microsomal PGE2 synthase-1 as a molecular target of curcumin and we show that inhibition of microsomal PGE2 synthase-1 activity is the predominant mechanism of curcumin to suppress PGE2 biosynthesis. Curcumin reversibly inhibited the conversion of PGH2 to PGE2 by microsomal PGE2 synthase-1 in microsomes of interleukin-1β–stimulated A549 lung carcinoma cells with an IC50 of 0.2 to 0.3 μmol/L. Closely related polyphenols (e.g., resveratrol, coniferyl alcohol, eugenol, rosmarinic acid) failed in this respect, and isolated ovine COX-1 and human recombinant COX-2 were not inhibited by curcumin up to 30 μmol/L. In lipopolysaccharide-stimulated human whole blood, curcumin inhibited COX-2–derived PGE2 formation from endogenous or from exogenous arachidonic acid, whereas the concomitant formation of COX-2–mediated 6-keto PGF1α and COX-1–derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid was suppressed only at significant higher concentrations. Based on the key function of PGE2 in inflammation and carcinogenesis, inhibition of microsomal PGE2 synthase-1 by curcumin provides a molecular basis for its anticarcinogenic and anti-inflammatory activities. [Mol Cancer Ther 2009;8(8):2348–55]
Identification of Human Cathepsin G As a Functional Target of Boswellic Acids from the Anti-Inflammatory Remedy Frankincense
2009-08-01

Abstract Frankincense preparations, used in folk medicine to cure inflammatory diseases, showed anti-inflammatory effectiveness in animal models and clinical trials. Boswellic acids (BAs) constitute major pharmacological principles of frankincense, but their targets and the underlying molecular modes of action are still unclear. Using a BA-affinity Sepharose matrix, a 26-kDa protein was selectively precipitated from human neutrophils and identified as the lysosomal protease cathepsin G (catG) by mass spectrometry (MALDI-TOF) and by immunological analysis. In rigid automated molecular docking experiments BAs tightly bound to the active center of catG, occupying the same part of the binding site as the synthetic catG inhibitor JNJ-10311795 (2-[3-{methyl[1-(2-naphthoyl)piperidin-4-yl]amino}carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid). BAs potently suppressed the proteolytic activity of catG (IC50 of ∼600 nM) in a competitive and reversible manner. Related serine proteases were significantly less sensitive against BAs (leukocyte elastase, chymotrypsin, proteinase-3) or not affected (tryptase, chymase). BAs inhibited chemoinvasion but not chemotaxis of challenged neutrophils, and they suppressed Ca2+ mobilization in human platelets induced by isolated catG or by catG released from activated neutrophils. Finally, oral administration of defined frankincense extracts significantly reduced catG activities in human blood ex vivo vs placebo. In conclusion, we show that catG is a functional and pharmacologically relevant target of BAs, and interference with catG could explain some of the anti-inflammatory properties of frankincense.
Artemis
2009-08-01

A central feature of relational database management systems is the ability to define multiple different views over an underlying database schema. Views provide a method of defining access control to the underlying database, since a view exposes a part of the database and hides the rest. Views also provide logical data independence to application programs that access the database. For most cases, the process of specifying the desired views in SQL is typically tedious and error-prone. While numerous tools exist to support developers in debugging program code, we are not aware of any tool that supports developers in verifying the correctness of their views defined in SQL.
Andermann Syndrome can be a Phenocopy of Hereditary Motor and Sensory Neuropathy – Report of a Discordant Sibship with a Compound Heterozygous Mutation of theKCC3Gene
2009-08-01

Andermann syndrome is a rare autosomal recessive disorder characterized by agenesis of the corpus callosum (ACC), progressive motor-sensory neuropathy, mental retardation and facial features. We report on two siblings with the clinical picture of a demyelinating hereditary motor and sensory neuropathy (HMSN), where only the presence of ACC in the younger brother pointed to the diagnosis of Andermann syndrome. Mutation analysis of the KCC3 (SLC12A6) gene showed a compound heterozygous mutation; a maternal missense mutation c.1616G>A (p.G539D) and a paternal splice mutation c.1118+1G>A in both siblings. We hypothesize that mutations of the KCC3 gene may result in non-syndromic childhood onset HMSN.
Catheter-Based Delivery of Fluid Paclitaxel for Prevention of Restenosis in Native Coronary Artery Lesions After Stent Implantation
2009-08-01

Background-Stents eluting antiproliferative drugs reduce the incidence of restenosis but delay healing of the vascular wall.We assessed the safety and efficacy of catheter-based local delivery of fluid paclitaxel in patients with coronary de novo stenoses after implantation of a bare metal stent.Methods and Results-We conducted a prospective, randomized trial comparing the local delivery of fluid paclitaxel after bare metal stent implantation (group I) with the implantation of a bare metal stent (group II) and the implantation of a paclitaxel-eluting stent (group III) in 204 patients.The primary end point was in-stent late lumen loss.Secondary end points included binary restenosis rate Ͼ50%, minimal lumen diameter, diameter stenosis, and a composite clinical end point (major adverse cardiac events and revascularization of the target lesion) 6 months after intervention.At 6 months, angiography showed an in-stent late lumen loss of 0.61Ϯ0.44mm in group I versus 0.99Ϯ0.72 mm in group II (I versus II, Pϭ0.0006) and 0.44Ϯ0.48mm in group III (noninferiority of I versus III, Pϭ0.023).The 1-sided 95% CI for the true difference of the means of in-stent late lumen loss in groups I and III was Ϫρ to 0.3174188.The cumulative overall rate of major cardiac events was 13.4% in group I, 26.8% in group II, and 14.9% in group III.Target lesion revascularization rate was 13.4% (group I), 22.1% (group II), and 13.4% (group III).Conclusions-Additional antiproliferative treatment of de novo lesions in native coronary arteries with catheter-based delivery of fluid paclitaxel after bare metal stenting was safe and significantly reduced neointimal proliferation, restenosis, and clinical events compared with bare metal stent implantation alone.
Demonstration of an eye-movement-induced visual motion illusion (Filehne illusion) in Rhesus monkeys
2009-08-01

During pursuit eye movements, the world around us remains perceptually stable despite the retinal-image slip induced by the eye movement. It is commonly held that this perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. However, if the reference signal is too small or too large, a false eye-movement-induced motion of the external world, the Filehne illusion (FI), will be perceived. A reference signal of inadequate size can be simulated experimentally by asking human subjects to pursue a target across backgrounds with externally added motion that are perceived as moving. In the present study we asked if non-human primates respond to such manipulation in a way comparable to humans. Using psychophysical methods, we demonstrate that Rhesus monkeys do indeed experience a percept of pursuit-induced background motion. In this study we show that an FI can be predictably induced in Rhesus monkeys. The monkey FI shows dependencies on the size and direction of background movement, which is very similar to the ones characterizing the human FI. This congruence suggests that the perception of self-induced visual motion is based on similar inferential mechanisms in non-human and human primates.
Normalized Cross-Correlation using SOFT
2009-08-01

We present a novel method to compute the normalized cross-correlation (NCC) of spherical signals such as omnidirectional images for the purpose of image alignment, i.e. orientation estimation, or template tracking. Expanding the reference image and the search template in the spherical harmonics basis, we use the Fourier representation of SO(3) as introduced by Kostelec and Rockmore. We show that the normalized version of the cross-correlation function with regard to orientation can be expressed in terms of standard correlation terms and the NCC can therefore be computed efficiently in O (N <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> log <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (N)). The approach is validated with experiments on real image sequences in a template matching application.
Hexyl aminolevulinate fluorescence cystoscopy in bladder cancer
2009-08-01

Although bladder cancer occurs frequently, early diagnosis and complete removal of malignant lesions usually lead to good clinical outcomes. In the USA, white light cystoscopy (WLC) is commonly used for bladder cancer diagnosis and guidance of the surgical resection. However, with WLC malignant and precancerous lesions may be missed, resulting in a high rate of disease recurrence. Monitoring for and treating these recurrences carry high direct and indirect costs. Because hexyl aminolevulinate (HAL; 5-ALA-hexylester) fluorescence cystoscopy has greater sensitivity than WLC, especially for detecting early stage lesions, and its use provides more complete resection and lower disease recurrence, it has been recommended in European clinical guidelines. This article reports our own HAL experiences and first time recurrence data, describes how HAL was developed, provides key clinical trial results, and discusses how HAL, which has revolutionized fluorescence cystoscopy and bladder cancer care in Europe, may ultimately revolutionize bladder cancer care in the USA.
Estimate of the magnetic field of Mars based on the magnetic characteristics of the Yamato 000593 nakhlite
2009-08-01

Abstract— Yamato 000593, a nakhlite, was analyzed in terms of its magnetic record and magnetomineralogy. The natural remanent magnetization (NRM: 3.55–6.07 times 10 −5 Am 2 /kg) was thermally demagnetized at ∼320 °C, and it was unstable against alternating field demagnetization. Based on analyses of thermomagnetic curves, the temperature dependence of hysteresis parameters, and microscopic observations, the magnetic minerals mainly consist of magnetite (0.68 wt% of the sample, including ∼5% Fe 2 TiO 4 ) of less than 100 μm in size, associated with minor amounts of monoclinic pyrrhotite (&lt;0.069 wt% of the sample) and goethite. Thermal demagnetization of NRM at ∼330 °C is explained due to an offset of magnetization of antipodal NRM components of magnetite, whereas it is not due to a pyrrhotite Curie point. Large magnetite grains show exsolution texture with ilmenite laths, and are cut by silicate (including goethite) veins that formed along cracks. Numerous single‐domain (SD) and pseudo‐single‐domain (PSD) magnetite grains are scattered in the mesostasis and adjacent olivine grains. Moderate coercive forces of H C = 6.8 mT and H RC = 31.1 mT suggest that Yamato 000593 is fundamentally able to carry a stable NRM; however, NRM was found to be unstable. Accordingly, the meteorite was possibly crystallized at 1.3 Ga under an extremely weak or absent magnetic field, or was demagnetized by impact shock at 12 Ma (ejection age) on Mars. This finding differs from the results of previous paleomagnetic studies of SNC (shergottites, nakhlites, chassignites, and orthopyroxenite) Martian meteorites. The significant dipole magnetic field resulting from the molten metallic core was probably absent during the Amazonian Epoch (after 1.8 Ga) on Mars.
Cardiac CT in 2009.
2009-08-01

Multislice computed tomography is an emerging diagnostic modality in cardiology practice. Within the last decade a rapid technical evolution from 4-slice scanners to 64-slice and meanwhile 320-slice scanners which faster gantry rotation time has taken place. These advances as well as improved post-processing tools account for a stabilization of image quality and allow assessing cardiac structures with high spatial and temporal resolution. Moreover, dedicated acquisition techniques have been employed to reduce radiation exposure to a minimum. Today cardiac computed tomography is not only able to depict the coronary arteries, but to get reliable information about cardiac function and cardiac structure. This review focuses on present clinical indications and future application of multi-slice computed tomography in clinical cardiology.
The ANP/cGMP/cGMP-dependent protein kinase pathway counteracts Angiotensin II-stimulated calcium mobilization in cardiac myocytes
2009-08-01

Background The cardiac hormone atrial natriuretic peptide (ANP) exerts local, Guanylyl Cyclase-A (GC-A) – mediated myocardial effects to antagonize the Cai-dependent hypertrophic growth response to Angiotensin II (Ang II). The present study aimed to characterize the specific molecular mechanisms mediating the reciprocal interactions between the ANP/GC-A and the Ang II/AT1 systems in the heart.
The PKG1 specific phosphorylation substrate cysteine-rich protein 2 knockout decreases blood pressure and intimal hyperplasia
2009-08-01

The cysteine-rich protein 2 has previously been suggested as a novel target of PKG1. Cysteine-rich proteins (CRP) are evolutionarily conserved proteins that define a subset of zinc-binding LIM domain proteins. This family of LIM domain proteins originally included three members (CRP1, CRP2/SLIM, CRP3/MLP). Previously, a new member of the CRP family was identified through a yeast two hybrid screen using PKG1 as bait. This protein was initially named CRP2. Subsequently, based on structural and sequence similarities, and because it is the product of a distinct gene and not an ortholog of CRP2/smLIM this new CRP2 was grouped into the CRP1, CRP2/SLIM, CRP3/MLP subset of LIM domain proteins and is also referred to as CRP4. CRP4 is expressed in laminas I and II of the mouse spinal cord and is colocalized with PKG1 and the dorsal root ganglion (DRG) marker proteins calcitonin gene-related peptide, isolectin B4 and peripherin. CRP4 is phosphorylated in a cGMP-dependent manner, and its expression increases in the spinal cord and in DRGs after noxious stimulation of a hindpaw. CRP4-/- mice show increased nociceptive behavior in models of inflammatory hyperalgesia compared to wild-type mice. Intrathecal administration of cGMP analogs increases the nociceptive behavior in wild-type but not in CRP4-/- mice, indicating that the presence of CRP4 is important for cGMP-mediated nociception. CRP4 has been suggested as a new effector of PKG1-mediated spinal nociceptive processing and point to an inhibitory role of CRP2 in the generation of inflammatory pain.
The most oxygen-poor planetary nebula: AGB nucleosynthesis at low metallicities
2009-08-01

Abstract TS01 is an exceptional planetary nebula (PN) in the Galactic halo: it is the most oxygen-poor and has a double-degenerate core with mass close to 1.4M ⊙ , possibly a Supernova Ia progenitor. With data from the far UV to the IR we can pin down the abundances of half a dozen of elements. The oxygen abundance is by 1.9(±0.3) dex lower than in the Sun. Standard AGB models with appropriate mass and metallicity cannot explain the observed chemical composition. We find that additional mixing, induced by stellar rotation and/or by the presence of the close companion can explain most of the features of the abundance pattern in TS01.
The oncogenic potential of a bystander
2009-08-01

Commentary to: Caveolin-1 regulates EGFR signaling in MCF-7 breast cancer cells and enhances gefitinib-induced tumor cell inhibition Sophia Agelaki, Maria Spiliotaki, Harris Markomanolaki, Galatea Kallergi, Dimitris Mavroudis, Vassilis Georgoulias, Christos Stournaras
Dissociation Between Fatty Liver and Insulin Resistance in Humans Carrying a Variant of the Patatin-Like Phospholipase 3 Gene
2009-08-03

OBJECTIVE In a genome-wide association scan, the rs738409 C&amp;gt;G single nucleotide polymorphism (SNP) in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat but not with insulin resistance estimated from fasting values. We investigated whether the SNP determines liver fat independently of visceral adiposity and whether it may even play a role in protecting from insulin resistance. RESEARCH DESIGN AND METHODS Liver fat was measured by 1H magnetic resonance spectroscopy and total and visceral fat by magnetic resonance tomography in 330 subjects. Insulin sensitivity was estimated during an oral glucose tolerance test and the euglycemic-hyperinsulinemic clamp (n = 222). PNPLA3 and tumor necrosis factor-α mRNA and triglyceride content were measured in liver biopsies from 16 subjects. RESULTS Liver fat correlated strongly with insulin sensitivity (P &amp;lt; 0.0001) independently of age, sex, total fat, and visceral fat. G allele carriers of the SNP rs738409 had higher liver fat (P &amp;lt; 0.0001) and an odds ratio of 2.38 (95% CI 1.37–4.20) for having fatty liver compared to C allele homozygotes. Interestingly, insulin sensitivity (oral glucose tolerance test: P = 0.99; clamp: P = 0.32), serum C-reactive protein levels, lipids, or liver enzymes (all P &amp;gt; 0.14) were not different among the genotypes. Additional adjustment for liver fat actually revealed increased insulin sensitivity in more obese carriers of the G allele (P = 0.01). In liver biopsies triglyceride content correlated positively with expression of the proinflammatory gene tumor necrosis factor-α in C allele homozygotes (n = 6, P = 0.027) but not in G allele carriers (n = 10, P = 0.149). CONCLUSIONS PNPLA3 may be an important key to understand the mechanisms discriminating fatty liver with and without metabolic consequences.
Ecophysiology and the energetic benefit of mixotrophic Fe(II) oxidation by various strains of nitrate-reducing bacteria
2009-08-03

In order to assess the importance of nitrate-dependent Fe(II) oxidation and its impact on the growth physiology of dominant Fe oxidizers, we counted these bacteria in freshwater lake sediments and studied their growth physiology. Most probable number counts of nitrate-reducing Fe(II)-oxidizing bacteria in the sediment of Lake Constance, a freshwater lake in Southern Germany, yielded about 10(5) cells mL(-1) of the total heterotrophic nitrate-reducing bacteria, with about 1% (10(3) cells mL(-1)) of nitrate-reducing Fe(II) oxidizers. We investigated the growth physiology of Acidovorax sp. strain BoFeN1, a dominant nitrate-reducing mixotrophic Fe(II) oxidizer isolated from this sediment. Strain BoFeN1 uses several organic compounds (but no sugars) as substrates for nitrate reduction. It also reduces nitrite, dinitrogen monoxide, and O(2), but cannot reduce Fe(III). Growth experiments with cultures amended either with acetate plus Fe(II) or with acetate alone demonstrated that the simultaneous oxidation of Fe(II) and acetate enhanced growth yields with acetate alone (12.5 g dry mass mol(-1) acetate) by about 1.4 g dry mass mol(-1) Fe(II). Also, pure cultures of Pseudomonas stutzeri and Paracoccus denitrificans strains can oxidize Fe(II) with nitrate, whereas Pseudomonas fluorescens and Thiobacillus denitrificans strains did not. Our study demonstrates that nitrate-dependent Fe(II) oxidation contributes to the energy metabolism of these bacteria, and that nitrate-dependent Fe(II) oxidation can essentially contribute to anaerobic iron cycling.
Wide-field and two-photon imaging of brain activity with voltage- and calcium-sensitive dyes
2009-08-03

This review presents three examples of using voltage- or calcium-sensitive dyes to image the activity of the brain. Our aim is to discuss the advantages and disadvantages of each method with particular reference to its application to the study of the brainstem. Two of the examples use wide-field (one-photon) imaging; the third uses two-photon scanning microscopy. Because the measurements have limited signal-to-noise ratio, the paper also discusses the methodological aspects that are critical for optimizing the signal. The three examples are the following. (i) An intracellularly injected voltage-sensitive dye was used to monitor membrane potential in the dendrites of neurons in in vitro preparations. These experiments were directed at understanding how individual neurons convert complex synaptic inputs into the output spike train. (ii) An extracellular, bath application of a voltage-sensitive dye was used to monitor population signals from different parts of the dorsal brainstem. We describe recordings made during respiratory activity. The population signals indicated four different regions with distinct activity correlated with inspiration. (iii) Calcium-sensitive dyes can be used to label many individual cells in the mammalian brain. This approach, combined with two-photon microscopy, made it possible to follow the spike activity in an in vitro brainstem preparation during fictive respiratory rhythms. The organic voltage- and ion-sensitive dyes used today indiscriminatively stain all of the cell types in the preparation. A major effort is underway to develop fluorescent protein sensors of activity for selectively staining individual cell types.
Bladder cancer: work in progress
2009-08-03

Department of Urology, Eberhard-Karls-University Tuebingen, Tuebingen, Germany Correspondence to Arnulf Stenzl, MD, Professor and Chairman, Department of Urology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany Tel: +49 7071 2986613; fax: +49 7071 295092; e-mail: [email protected]
Early sacral neuromodulation prevents urinary incontinence after complete spinal cord injury
2009-08-04

Abstract Background The study aim was to investigate potential influences on human nerves and pelvic organs through early implantation of bilateral sacral nerve modulators (SNMs) in complete spinal cord injury (SCI) patients during the acute bladder‐areflexia phase. Methods Ten patients with neurologically‐confirmed complete spinal cord lesions (SCLs) were provided with bilateral SNMs during the phase of atonic‐detrusor muscle. Modulation was achieved by two electrodes implanted into each S 3 ‐foramen. Six patients declined and served as controls. The mean follow‐up was 26.2 months. Results Videourodynamics (VU) confirmed detrusor acontractility, resulting in urinary continence as well as significant reductions in urinary tract infections (UTIs). Bowel movements did not require oral laxatives; additional preprogrammed parameters achieved erections for intercourse. Interpretation Early SNM implantation in SCI patients may revolutionize neurogenic lower urinary tract (LUT) dysfunction management; it prevented detrusor overactivity and urinary incontinence, ensured normal bladder capacity, reduced UTI rates, and improved bowel and erectile functionality without nerve damage. Conclusion Future SCI investigations will be conducted to evaluate the potential benefits of even earlier SNM placement to progressively enhance pelvic organ functionality. This new approach may provide important clues required for assessing whether neuronal information is passed through the sympathetic trunk ganglion to the brain after complete SCI. Further investigations are needed to determine if functional magnetic resonance imaging (fMRI) might be helpful for analyzing changes in brain function in patients with SNMs and those taking antimuscarinics. ANN NEUROL 2010;67:74–84