julilili42/papers huggingface dataset:
Saturated, but Not Unsaturated, Fatty Acids Induce Apoptosis of Human Coronary Artery Endothelial Cells via Nuclear Factor-κB Activation
2006-10-25

High nonesterified fatty acid (NEFA) concentrations, as observed in the metabolic syndrome, trigger apoptosis of human umbilical vein endothelial cells. Since endothelial apoptosis may contribute to atherothrombosis, we studied the apoptotic susceptibility of human coronary artery endothelial cells (HCAECs) toward selected NEFAs and the underlying mechanisms. HCAECs were treated with single or combined NEFAs. Apoptosis was quantified by flow cytometry, nuclear factor κB (NFκB) activation by electrophoretic mobility shift assay, and secreted cytokines by enzyme-linked immunosorbent assay. Treatment of HCAECs with saturated NEFAs (palmitate and stearate) increased apoptosis up to fivefold (P &amp;lt; 0.05; n = 4). Unsaturated NEFAs (palmitoleate, oleate, and linoleate) did not promote apoptosis but prevented stearate-induced apoptosis (P &amp;lt; 0.05; n = 4). Saturated NEFA-induced apoptosis neither depended on ceramide formation nor on oxidative NEFA catabolism. However, NEFA activation via acyl-CoA formation was essential. Stearate activated NFκB and linoleate impaired stearate-induced NFκB activation. Pharmacological inhibition of NFκB and inhibitor of κB kinase (IKK) also blocked stearate-induced apoptosis. Finally, the saturated NEFA effect on NFκB was not attributable to NEFA-induced cytokine production. In conclusion, NEFAs display differential effects on HCAEC survival; saturated NEFAs (palmitate and stearate) are proapoptotic, and unsaturated NEFAs (palmitoleate, oleate, and linoleate) are antilipoapoptotic. Mechanistically, promotion of HCAEC apoptosis by saturated NEFA requires acyl-CoA formation, IKK, and NFκB activation.
The “Azido Gauche Effect”Implications for the Conformation of Azidoprolines
2006-10-25

The "azido gauche effect" was examined both experimentally and theoretically and was found to determine the conformation of, for example, (4R)- and (4S)-azidoproline (Azp) derivatives. For (4R)Azp derivatives, the azido gauche effect induces a preferred C(4)-exo conformation of the pyrrolidine ring, which leads to stabilization of the s-trans amide conformer of, e.g., Ac-(4R)Azp-OCH(3) (5R) via an n-->pi interaction between the nonbonding electrons of the oxygen of the acetyl group and the carbonyl group of the ester. For (4S)Azp derivatives, the azido gauche effect results in a C(4)-endo conformation of the pyrrolidine ring that does not allow for this stabilizing n-->pi interaction of the s-trans conformer. Consequently, a significantly higher s-trans:s-cis amide conformer ratio is observed for (4R)Azp compared to (4S)Azp derivatives (e.g., 6.1:1 versus 2.6:1 in D(2)O for Ac-(4R)Azp-OCH(3) (5R) compared to Ac-(4S)Azp-OCH(3) (5S)). These conformational preferences are reflected in the higher tendency of (4S)Azp-containing peptides to form cyclic peptides with all-cis amide bonds compared to (4R)Azp derivatives. Ab initio calculations demonstrate that the strength of the azido gauche effect is comparable to that of the well-known "fluorine gauche effect". For azidoethane derivatives N(3)-CH(2)CH(2)-X (X = N(3), NHCOH, NHAc, or N(CH(3))Ac), the ab initio calculations revealed energy differences of 5-13 kJ mol(-)(1) between the anti and gauche conformations in favor of the gauche conformer. Calculations were also performed for the (4R)Azp and (4S)Azp derivatives 5R and 5S, supporting the experimentally observed data.
Phosphenes Electrically Evoked with DTL Electrodes: A Study in Patients with Retinitis Pigmentosa, Glaucoma, and Homonymous Visual Field Loss and Normal Subjects
2006-10-25

Use of DTL electrodes to elicit electrical phosphenes is safe, fast, and reliable. It bears significant advantages over corneal electrodes and provides a valuable tool to elucidate ophthalmologic disease processes and to screen candidates for retinal prostheses.
Primate Area MST-l Is Involved in the Generation of Goal-Directed Eye and Hand Movements
2006-10-25

The contributions of the middle superior temporal area (MST) in the posterior parietal cortex of rhesus monkeys to the generation of smooth-pursuit eye movements as well as the contributions to motion perception are well established. Here, we present the first experimental evidence that this area also contributes to the generation of goal-directed hand movements toward a moving target. This evidence is based on the outcome of intracortical microstimulation experiments and transient lesions by small injections of muscimol at identified sites within the lateral part of area MST (MST-l). When microstimulation was applied during the execution of smooth-pursuit eye movements, postsaccadic eye velocity in the direction of the preferred direction of the stimulated site increased significantly (in 93 of 136 sites tested). When microstimulation was applied during a hand movement trial, the hand movement was displaced significantly in the same direction (in 28 of 39 sites tested). When we lesioned area MST-l transiently by injections of muscimol, steady-state eye velocity was exclusively reduced for ipsiversive smooth-pursuit eye movements. In contrast, hand movements were displaced toward the contralateral side, irrespective of the direction of the moving target. Our results provide evidence that area MST-l is involved in the processing of moving targets and plays a role in the execution of smooth-pursuit eye movements as well as visually guided hand movements.
(4R)-4-Hydroxy-1-[(2S)-2-hydroxydodecyl]-L-proline monohydrate
2006-10-25

The title compound, C17H33NO4·H2O, was found to be the S diastereoisomer with respect to the asymmetric C atom at the OH group on the chain. The X-ray structure was determined as part of a study of the molecular geometry and stereochemistry of l-proline derivatives for pre-coating thin-layer chromatography plates intended for enantiomeric separation.
Phospholipase A2 Activity-Dependent Stimulation of Ca 2+ Entry by Human Parvovirus B19 Capsid Protein VP1
2006-10-28

ABSTRACT Recent reports demonstrated an association of human parvovirus B19 with inflammatory cardiomyopathy (iCMP), which is accompanied by endothelial dysfunction. As intracellular Ca 2+ activity is a key regulator of cell function and participates in mechanisms leading to endothelial dysfunction, the present experiments explored the effects of the B19 capsid proteins VP1 and VP2. A secreted phospholipase A2 (PLA2)-like activity has been located in the VP1 unique region of the B19 minor capsid protein. As PLA2 has recently been shown to activate the store-operated or capacitative Ca 2+ channel I CRAC , we analyzed the impact of the viral PLA2 motif on Ca 2+ entry. We cloned the VP1 and VP2 genes isolated from a patient suffering from fatal B19 iCMP into eukaryotic expression vectors. We also generated a B19 replication-competent plasmid to demonstrate PLA2 activity under the control of the complete B19 genome. After the transfection of human endothelial cells (HMEC-1), cytosolic Ca 2+ activity was determined by utilizing Fura-2 fluorescence. VP1 and VP2 expression did not significantly modify basal cytosolic Ca 2+ activity or the decline of cytosolic Ca 2+ activity following the removal of extracellular Ca 2+ . However, expression of VP1 and of the full-length B19 clone, but not of VP2, significantly accelerated the increase of cytosolic Ca 2+ activity following the readdition of extracellular Ca 2+ in the presence of thapsigargin, indicating an activation of I CRAC. The effect of VP1 was mimicked by the PLA2 product lysophosphatidylcholine and abolished by an inactivating mutation of the PLA2-encoding region of the VP1 gene. Our observations point to the activation of Ca 2+ entry by VP1 PLA2 activity, an effect likely participating in the pathophysiology of B19 infection.
Distorted Relation between mRNA Copy Number and Corresponding Major Histocompatibility Complex Ligand Density on the Cell Surface
2006-10-30

The major histocompatibility complex (MHC) presents peptides derived from degraded cellular proteins to T-cells and is thus crucial for triggering specific immune responses against viral infections or cancer. Up to now, there has been no evidence for a correlation between levels of mRNA (the "transcriptome") and the density of MHC-peptide complexes (the "MHC ligandome") on cells. Because such dependences are of intrinsic importance for the detailed understanding of translation efficiency and protein turnover and thus for systems biology in general and for tumor immunotherapy in practical application, we quantitatively analyzed the levels of mRNA and corresponding MHC ligand densities in samples of renal cell carcinomas and their autologous normal kidney tissues. Relative quantification was carried out by gene chip analysis and by stable isotope peptide labeling, respectively. In comparing more than 270 pairs of gene expression and corresponding peptide presentation ratios, we demonstrate that there is no clear correlation (r = 0.32) between mRNA levels and corresponding MHC peptide levels in renal cell carcinoma. A significant number of peptides presented predominantly on tumor or normal tissue showed no or only minor changes in mRNA expression levels. In several cases, peptides could even be identified despite the virtual absence of the respective mRNA. Thus we conclude that a majority of epitopes from tumor-associated antigens will not be found in approaches based mainly on mRNA expression studies as mRNA expression reflects a distorted picture of the situation on the cell surface as visible for T-cells.
Computer modelling of the energies and vibrational properties of hydroxyl groups in - and -Mg2SiO4
2006-10-30

The structure, formation energies and infrared (IR) active vibrational modes of hydrous defects in the iron free end members of two of the most important minerals of the Earth's mantle, alpha- and beta-Mg2SiO4, are studied by atomic-scale computational modelling in order to identify the hydrogen incorporation mechanism observed in experiment. Two computational methods are used; calculations based on inter-atomic potentials provide information on all defect configuration in the two minerals, and a combined quantum mechanical/molecular mechanics embedded cluster method is used to validate selected results. For forsterite (alpha-Mg2SiO4), the results suggest that IR bands at low frequencies (wavenumbers 3000-3250 cm(-1)) are related to protons populating M1 vacancies. Despite the unfavourable creation of silicon vacancies, calculated medium- and high-frequency IR bands are linked to protons occupying vacant Si sites. For iron-free wadsleyite (beta-Mg2SiO4) IR frequencies for hydrated cation vacancies have been calculated for the first time. The main doublet at 3360-3326 cm(-1) is attributed to two OH groups located in a vacant M3 site. IR bands at higher wavenumber such as the anisotropic doublet at 3615-3580 cm(-1) appear to be linked to OH in vacant Si sites. Low accuracy on the calculated frequencies does not permit a strict and rigorous assignment of each individual IR band observed in hydrous forsterite and wadsleyite. However, it does allow the identification of the most favourable site for protonation and provides a useful approximation to the corresponding IR stretching frequencies for a given hydrogen incorporation mechanisms in these nominally anhydrous silicate structures.
Kernel Based Functional Gene Grouping
2006-10-30

During the last years, high throughput experiments have become very popular. During the analysis of such data the need for a functional grouping of genes arises. In this paper, we propose grouping genes according to their biological function by means of kernel functions, which are similarity measures having special mathematical properties and play a crucial role e.g. in SVM classification. Thereby our kernel functions rely on functional information on the genes provided by Gene Ontology annotation. We investigate and compare several provably symmetric, positive semidefinite kernel functions in combination with spectral clustering, dual k-means and average linkage and demonstrate that our approach leads to good clustering results.
Platelets induce differentiation of human CD34 + progenitor cells into foam cells and endothelial cells
2006-10-31

Recruitment of human CD34 + progenitor cells toward vascular lesions and differentiation into vascular cells has been regarded as a critical initial step in atherosclerosis. Previously we found that adherent platelets represent potential mediators of progenitor cell homing besides their role in thrombus formation. On the other hand, foam cell formation represents a key process in atherosclerotic plaque formation. To investigate whether platelets are involved in progenitor cell recruitment and differentiation into endothelial cells and foam cells, we examined the interactions of platelets and CD34 + progenitor cells. Cocultivation experiments showed that human platelets recruit CD34 + progenitor cells via the specific adhesion receptors P‐selectin/PSGL‐1 and β 1 ‐ and β 2 ‐integrins. Furthermore, platelets were found to induce differentiation of CD34 + progenitor cells into mature foam cells and endothelial cells. Platelet‐induced foam cell generation could be prevented partially by HMG coenzyme A reductase inhibitors via reduction of matrix metallo‐proteinase‐9 (MMP‐9) secretion. Finally, agonists of peroxisome proliferator‐activated receptor‐α and ‐γ attenuated platelet‐induced foam cell generation and production of MMP‐9. The present study describes a potentially important mechanism of platelet‐induced foam cell formation and generation of endothelium in atherogenesis and atheroprogression. The understanding and modulation of these mechanisms may offer new treatment strategies for patients at high risk for atherosclerotic diseases.—Daub, K., Langer, H., Seizer, P., Stellos, K., May, A. E., Goyal, P., Bigalke, B., Schönberger, T., Geisler, T., Siegel‐Axel, D., Oostendorp, R. A. J., Lindemann, S., Gawaz, M. Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells. FASEB J. 20, E1935–E1944 (2006)
Role of proton MR for the study of muscle lipid metabolism
2006-10-31

Abstract 1 H‐MR spectroscopy (MRS) of intramyocellular lipids (IMCL) became particularly important when it was recognized that IMCL levels are related to insulin sensitivity. While this relation is rather complex and depends on the training status of the subjects, various other influences such as exercise and diet also influence IMCL concentrations. This may open insight into many metabolic interactions; however, it also requires careful planning of studies in order to control all these confounding influences. This review summarizes various historical, methodological, and practical aspects of 1 H‐MR spectroscopy (MRS) of muscular lipids. That includes a differentiation of bulk magnetic susceptibility effects and residual dipolar coupling that can both be observed in MRS of skeletal muscle, yet affecting different metabolites in a specific way. Fitting of the intra‐ (IMCL) and extramyocellular (EMCL) signals with complex line shapes and the transformation into absolute concentrations is discussed. Since the determination of IMCL in muscle groups with oblique fiber orientation or in obese subjects is still difficult, potential improvement with high‐resolution spectroscopic imaging or at higher field strength is considered. Fat selective imaging is presented as a possible alternative to MRS and the potential of multinuclear MRS is discussed. 1 H‐MRS of muscle lipids allows non‐invasive and repeated studies of muscle metabolism that lead to highly relevant findings in clinics and patho‐physiology. Copyright © 2006 John Wiley &amp; Sons, Ltd.
Potassium Channels‐Mediated Vasorelaxation of Rat Aorta Induced by Resveratrol
2006-10-31

Abstract: Resveratrol, a phenolic substance present in grapes and a variety of medical plants, has been reported to induce vasorelaxation, however the mechanisms are uncertain. In this paper we investigate the possible participation of K + channels in the endothelium‐independent vasodilatation of rat aorta induced by resveratrol. Resveratrol induced concentration‐dependent relaxation of rings with endothelium and without endothelium. We used different potassium channel inhibitors to determine whether the K + channels mediated endothelium‐independent relaxation of rat aorta induced by resveratrol. Highly selective blocker of ATP‐sensitive K + channels, glibenclamide, as well as non‐selective blockers of K + channels, tetraethylammonium, did not block resveratrol‐induced relaxation of rat aortic rings. Charybdotoxin, a blocker of calcium‐sensitive K + channels did not affect the resveratrol‐induced relaxation. 4‐Aminopiridine, non‐selective blocker of voltage‐gated K + (Kv) channels, and margatoxin that inhibits Kv1 channels abolished relaxation of rat aortic rings induced by resveratrol. In conclusion, we have shown that resveratrol potently relaxed rat aortic rings with denuded endothelium. It seems that 4‐aminopiridine and margatoxin‐sensitive K + channels located in the smooth muscle of rat aorta mediated this relaxation.
Influence of polymorphisms in xenobiotic‐metabolizing genes and DNA‐repair genes on diepoxybutane‐induced SCE frequency
2006-10-31

Abstract Analysis of the combined effects of polymorphisms in genes encoding xenobiotic metabolizing enzymes (XMEs) and DNA repair proteins may be a key to understanding the role of these genes in the susceptibility of individuals to mutagens. In the present study, we performed an in vitro experiment on lymphocytes from 118 healthy donors that measured the frequency of diepoxybutane (DEB) induced sister chromatid exchanges (SCEs) in relation to genetic polymorphisms in genes coding for XMEs ( CYP1A1, CYP2E1, GSTT1, EPHX, and NAT2), as well as DNA repair proteins (X RCC1, XRCC2, XRCC3, XPD, XPA, XPC, XPG, XPF, ERCC1, BRCA1, NBS1, and RAD51 ). We found that GSTT1 (−) and CYP2E1 c1/c2 polymorphisms were associated with higher DEB‐induced SCE frequencies, and that NAT2 G 590 A was associated with lower SCE induction by DEB. Analysis of the effect of pairs of genes showed that for a fixed GSTT1 genotype, the SCE level increased with an increasing number of Tyr alleles in EPHX codon 113. We found that among GSTT1 (+) individuals the DEB‐induced SCE level was significantly lower when the EPHX 139 codon was His/Arg rather than His/His. An interaction between polymorphisms in CYP2E1 and at EPHX codon 113 was also observed. The results of our study confirm observations in cancer patients and in people exposed to xenobiotics indicating that sensitivity to mutagens depends upon a combined effect of a variety of “minor impact” genes. Moreover, our results indicate that polymorphisms in genes coding for XMEs have a greater influence on the genotoxic activity of DEB, measured by DEB‐induced SCE frequency, than polymorphisms in genes encoding DNA repair proteins. Environ. Mol. Mutagen. 47:, 2006. © 2006 Wiley‐Liss, Inc.
Subcellular Trafficking of the Arabidopsis Auxin Influx Carrier AUX1 Uses a Novel Pathway Distinct from PIN1
2006-11-01

Abstract The directional flow of the plant hormone auxin mediates multiple developmental processes, including patterning and tropisms. Apical and basal plasma membrane localization of AUXIN-RESISTANT1 (AUX1) and PIN-FORMED1 (PIN1) auxin transport components underpins the directionality of intercellular auxin flow in Arabidopsis thaliana roots. Here, we examined the mechanism of polar trafficking of AUX1. Real-time live cell analysis along with subcellular markers revealed that AUX1 resides at the apical plasma membrane of protophloem cells and at highly dynamic subpopulations of Golgi apparatus and endosomes in all cell types. Plasma membrane and intracellular pools of AUX1 are interconnected by actin-dependent constitutive trafficking, which is not sensitive to the vesicle trafficking inhibitor brefeldin A. AUX1 subcellular dynamics are not influenced by the auxin influx inhibitor NOA but are blocked by the auxin efflux inhibitors TIBA and PBA. Furthermore, auxin transport inhibitors and interference with the sterol composition of membranes disrupt polar AUX1 distribution at the plasma membrane. Compared with PIN1 trafficking, AUX1 dynamics display different sensitivities to trafficking inhibitors and are independent of the endosomal trafficking regulator ARF GEF GNOM. Hence, AUX1 uses a novel trafficking pathway in plants that is distinct from PIN trafficking, providing an additional mechanism for the fine regulation of auxin transport.
An overview of the higher level classification of Pucciniomycotina based on combined analyses of nuclear large and small subunit rDNA sequences
2006-11-01

In this study we provide a phylogenetically based introduction to the classes and orders of Pucciniomycotina (= Urediniomycetes), one of three subphyla of Basidiomycota. More than 8000 species of Pucciniomycotina have been described including putative saprotrophs and parasites of plants, animals and fungi. The overwhelming majority of these (approximately 90%) belong to a single order of obligate plant pathogens, the Pucciniales (= Uredinales), or rust fungi. We have assembled a dataset of previously published and newly generated sequence data from two nuclear rDNA genes (large subunit and small subunit) including exemplars from all known major groups in order to test hypotheses about evolutionary relationships among the Pucciniomycotina. The utility of combining nuc-lsu sequences spanning the entire D1-D3 region with complete nuc-ssu sequences for resolution and support of nodes is discussed. Our study confirms Pucciniomycotina as a monophyletic group of Basidiomycota. In total our results support eight major clades ranked as classes (Agaricostilbomycetes, Atractiellomycetes, Classiculomycetes, Cryptomycocolacomycetes, Cystobasidiomycetes, Microbotryomycetes, Mixiomycetes and Pucciniomycetes) and 18 orders.
Diverse tulasnelloid fungi form mycorrhizas with epiphytic orchids in an Andean cloud forest
2006-11-01

The mycorrhizal state of epiphytic orchids has been controversially discussed, and the state and mycobionts of the pleurothallid orchids, occurring abundantly and with a high number of species on stems of trees in the Andean cloud forest, were unknown. Root samples of 77 adult individuals of the epiphytic orchids Stelis hallii, S. superbiens, S. concinna and Pleurothallis lilijae were collected in a tropical mountain rainforest of southern Ecuador. Ultrastructural evidence of symbiotic interaction was combined with molecular sequencing of fungi directly from the mycorrhizas and isolation of mycobionts. Ultrastructural analyses displayed vital orchid mycorrhizas formed by fungi with an imperforate parenthesome and cell wall slime bodies typical for the genus Tulasnella. Three different Tulasnella isolates were obtained in pure culture. Phylogenetic analysis of nuclear rDNA sequences from coding regions of the ribosomal large subunit (nucLSU) and the 5.8S subunit, including parts of the internal transcribed spacers, obtained directly from the roots and from the fungal isolates, yielded seven distinct Tulasnella clades. Tulasnella mycobionts in Stelis concinna were restricted to two Tulasnella sequence types while the other orchids were associated with up to six Tulasnella sequence types. All Tulasnella sequences are new to science and distinct from known sequences of mycobionts of terrestrial orchids. The results indicate that tulasnelloid fungi, adapted to the conditions on tree stems, might be important for orchid growth and maintenance in the Andean cloud forest.