julilili42/papers huggingface dataset:
Carbonyl reduction of naltrexone and dolasetron by oxidoreductases isolated from human liver cytosol
2004-11-18

Abstract The opioid receptor antagonist naltrexone and the antiemetic 5-HT3 receptor antagonist dolasetron are ketonic drugs that are efficiently reduced to their corresponding alcohols in-vivo. These experiments aimed at characterizing the role in these reactions of individual oxidoreductases present in human liver cytosol. Aldo-keto reductases (AKRs) and carbonyl reductase (CR, EC 1.1.1.184) purified from human liver cytosol were incubated with varying substrate concentrations and 6β-naltrexol or reduced dolasetron were analysed by HPLC. AKR1C1, AKR1C2, and AKR1C4 were able to reduce both substrates. On the basis of kcat/Km values, AKR1C4 was nearly 1000-fold more efficient in reducing naltrexone than was AKR1C1, while AKR1C2 was of intermediate efficiency. Substrate inhibition was observed on incubating AKR1C2 or AKR1C4 with naltrexone. In contrast, dolasetron was also a substrate of CR. AKR1C1 and AKR1C4 were the most efficient enzymes in producing reduced dolasetron. We concluded that the efficient reduction of naltrexone by AKR1C4 probably causes the high 6β-naltrexol/naltrexone ratio in man. The rapid disappearance from human plasma of dolasetron given intravenously and its virtual absence after oral dosage are explained by its liability to reduction by several enzymes, including CR which shows widespread expression in human tissues.
Variational solution of the Yang-Mills Schrödinger equation in Coulomb gauge
2004-11-19

The Yang-Mills Schr\\"odinger equation is solved in Coulomb gauge for the vacuum by the variational principle using an ansatz for the wave functional, which is strongly peaked at the Gribov horizon. A coupled set of Schwinger-Dyson equations for the gluon and ghost propagators in the Yang-Mills vacuum as well as for the curvature of gauge orbit space is derived and solved in one-loop approximation. We find an infrared suppressed gluon propagator, an infrared singular ghost propagator and a almost linearly rising confinement potential.
Subapical Localization of the Dopamine D3 Receptor in Proximal Tubules of the Rat Kidney
2004-11-19

The dopamine D 3 receptor (D 3 R), intensively studied in neuroscience, also plays an important role in the regulation of renal and cardiovascular function. In contrast to functional findings, less information is available on its localization in the kidney. Neither RT-PCR studies nor radioligand binding assays are suitable to selectively determine the distribution of renal D 3 R at the level of cellular or even subcellular structures. We studied the renal D 3 R distribution in Sprague-Dawley rats by a polyclonal antiserum directed against an epitope in the third intracytoplasmic loop. D 3 R immunoreactivity was detected by indirect immunofluorescence and confocal laser scanning microscopy. D 3 R staining was confined to the renal cortex and occurred in proximal convoluted tubules near or in direct connection with the urinary pole of the glomeruli. The fluorescent spots were restricted to the subapical portion of the proximal tubular cells. Double staining with the F-actin marker phalloidin revealed a localization of the D 3 R below the brush border region. However, staining by anti-P1/p2-adaptins, recognizing clathrin-coated compartments, did not correspond to the distribution of the D 3 R signal. This is the first description of a D 3 R accumulation in a cytoplasmic pool in the kidney, probably corresponding to a recycling mechanism or storage compartment.
Clonal Type I Interferon–producing and Dendritic Cell Precursors Are Contained in Both Human Lymphoid and Myeloid Progenitor Populations
2004-11-22

Because of different cytokine responsiveness, surface receptor, and transcription factor expression, human CD11c− natural type I interferon–producing cells (IPCs) and CD11c+ dendritic cells were thought to derive through lymphoid and myeloid hematopoietic developmental pathways, respectively. To directly test this hypothesis, we used an in vitro assay allowing simultaneous IPC, dendritic cell, and B cell development and we tested lymphoid and myeloid committed hematopoietic progenitor cells for their developmental capacity. Lymphoid and common myeloid and granulocyte/macrophage progenitors were capable of developing into both functional IPCs, expressing gene transcripts thought to be associated with lymphoid lineage development, and into dendritic cells. However, clonal progenitors for both populations were about fivefold more frequent within myeloid committed progenitor cells. Thus, in humans as in mice, natural IPC and dendritic cell development robustly segregates with myeloid differentiation. This would fit with natural interferon type I–producing cell and dendritic cell activity in innate immunity, the evolutionary older arm of the cellular immune system.
Megasonic-assisted development of nanostructures: Investigations on high aspect ratio nanoholes
2004-11-22

The influence of megasonic agitation on the development of nanostructures with high aspect ratio is investigated thoroughly. The improvements in homogeneity, depth, and quality of nanostructures are related to specific interactions of the sound wave with the resist and developer. Two phases in the development process are operative. The specific role of microstreaming providing physical supply of fresh developer is identified and the reduction of viscosity by megasonic interaction is derived. The advantage of megasonic agitation as a nondestructive development of high aspect ratio nanostructures is demonstrated.
Reorganization in congenital hemiparesis acquired at different gestational ages
2004-11-23

Abstract It is well established that the reorganizational potential of the developing human brain is superior to that of the adult brain, but whether age‐dependent differences exist already in the prenatal and perinatal period is not known. We have studied sensorimotor reorganization in 34 patients with congenital hemiparesis (age range, 5–27 years), using transcranial magnetic stimulation and functional magnetic resonance imaging during simple hand movements. Underlying pathologies were brain malformations (first and second trimester lesions; n = 10), periventricular brain lesions (early third trimester lesions; n = 12), and middle cerebral artery infarctions (late third trimester lesions; n = 12). Of this cohort, eight patients with malformations and all patients with periventricular lesions have been published previously. In all three groups of pathologies, transcranial magnetic stimulation identified patients in whom the paretic hand was controlled via ipsilateral corticospinal projections from the contralesional hemisphere (n = 16). In these patients, the motor dysfunction of the paretic hand correlated significantly with the timing period of the underlying brain lesion. This demonstrates that the efficacy of reorganization with ipsilateral corticospinal tracts indeed decreases during pregnancy. Ann Neurol 2004
Yersinia enterocoliticaInduces Apoptosis and Inhibits Surface Molecule Expression and Cytokine Production in Murine Dendritic Cells
2004-11-23

ABSTRACT Yersinia enterocolitica evades innate immunity by expression of a variety of pathogenicity factors. Therefore, adaptive immunity including CD4 + T cells plays an important role in defense against Y. enterocolitica . We investigated whether Y. enterocolitica might target dendritic cells (DC) involved in adaptive T-cell responses. For this purpose, murine DC were infected with Y. enterocolitica wild-type and mutant strains prior to incubation with ovalbumin (OVA) as antigen and 5-(6)-carboxyfluorescein diacetate N -succinimidyl ester-labeled OVA-specific T cells from DO11.10 mice. While T-cell proliferation was partially affected by infection of DC with plasmid-cured and YopP-deficient Yersinia mutant strains, no T-cell proliferation occurred after infection of DC with wild-type Y. enterocolitica . Infection of DC with Y. enterocolitica wild type resulted in decreased up-regulation of major histocompatibility complex class II, CD54 (intercellular adhesion molecule 1), CD 80, and CD86 expression. Experiments with plasmid-cured Y. enterocolitica or a YopP-deficient mutant strain revealed that YopP accounts for inhibition of surface molecule expression. Wild-type Y. enterocolitica suppressed the release of KC, tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-12 by DC, while infection of DC with plasmid-cured Y. enterocolitica or with the YopP-deficient mutant resulted in the production of these cytokines. Moreover, infection with wild-type Y. enterocolitica induced apoptosis in DC mediated by YopP. Apoptosis occurred despite translocation of NF-κB to the nucleus, as demonstrated by electromobility shift assays. Together, these data demonstrate that Y. enterocolitica targets functions of murine DC that are required for T-cell activation. This might contribute to evasion of adaptive immune responses by Y. enterocolitica .
AcDc – A new code for the NLTE spectral analysis of accretion discs: application to the helium CV AM CVn
2004-11-23

We present a recently developed code for detailed NLTE calculations of accretion disc spectra of cataclysmic variables and compact X-ray binaries. Assuming a radial structure of a standard alpha-disc, the disc is divided into concentric rings. For each disc ring the solution of the radiation transfer equation and the structure equations, comprising the hydrostatic and radiative equilibrium, the population of the atomic levels as well as charge and particle conservation, is done self-consistently. Metal-line blanketing and irradiation by the central object are taken into account. As a first application, we show the influence of different disc parameters on the disc spectrum for the helium cataclysmic variable AMCVn.
Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration
2004-11-24

Retina and retinal pigment epithelium (RPE) belong to the metabolically most active tissues in the human body. Efficient removal of acid load from retina and RPE is a critical function mediated by the choriocapillaris. However, the mechanism by which pH homeostasis is maintained is largely unknown. Here, we show that a functional complex of carbonic anhydrase 4 (CA4) and Na+/bicarbonate co-transporter 1 (NBC1) is specifically expressed in the choriocapillaris and that missense mutations in CA4 linked to autosomal dominant rod-cone dystrophy disrupt NBC1-mediated HCO3- transport. Our results identify a novel pathogenic pathway in which a defect in a functional complex involved in maintaining pH balances, but not expressed in retina or RPE, leads to photoreceptor degeneration. The importance of a functional CA4 for survival of photoreceptors implies that CA inhibitors, which are widely used as medications, particularly in the treatment of glaucoma, may have long-term adverse effects on vision.
Synthesis, characterization and optical limiting properties of a gallium phthalocyanine dimer
2004-11-24

A gallium phthalocyanine dimer with a direct gallium - gallium bond, [tBu(4)PcGa](2) . 2dioxane (2), has been synthesized and characterized by Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy, UV/Vis, IR, NMR and MALDI-MS. By EXAFS the gallium - gallium distance in 2 was found to be 2.46 Angstrom. Dimer 2 exhibits reverse saturable absorption with significantly reduced saturation intensity with respect to the starting material tBu(4)PcGaCl ( 1) as determined by means of optical limiting experiments.
Selective Complexation of N‐Alkylpyridinium Salts: Binding of NAD+ in Water
2004-11-24

Abstract A new class of receptor molecules is presented that is highly selective for N ‐alkylpyridinium ions and electron‐poor aromatics. Its key feature is the combination of a well‐preorganized molecular clip with an electron‐rich inner cavity and strategically placed, flanking bis‐phosphonate monoester anions. This shape and arrangement of binding sites attracts predominantly flat electron‐poor aromatics in water, binds them mainly by π–cation, π–π, CH–π, and hydrophobic interactions, and leads to their highly efficient desolvation. NAD + and NADP, the important cofactors of many redox enzymes, are recognized by the new receptor molecule, which embraces the catalytically active nicotinamide site and the adenine unit. Even nucleosides such as adenosine are likewise drawn into the clip's cavity. Complex formation and structures were examined by one‐ and two‐dimensional NMR spectroscopy, Job plot analyses, and isothermal titration microcalorimetric (ITC) measurements, as well as quantum chemical calculations of 1 H NMR shifts. The new receptor molecule is a promising tool for controlling enzymatic oxidation processes and for DNA chemistry.
[An already archived latent fingerprint as a DNA source for STR typing in a murder case].
2004-11-24

Former studies have shown that even a single skin contact, resulting in a latent fingerprint, can transfer enough DNA for genetic analysis. However, up to now latent fingerprints have usually not been used for DNA typing. In the present case the smeared trace of a hand was found in the suspect's car and archived. As it could not be evaluated in a classical manner, the evidence had to be examined by molecular genetic methods. DNA was extracted and typed in five different STR loci. Based on the yielded results, the significance of the findings is discussed.
Effects of co-activation on cortical organization and discrimination performance
2004-11-25

We used fMRI to investigate the effects of tactile co-activation on the topographic organization of the human primary somatosensory cortex (SI). Behavioral consequences of co-activation were studied in a psychophysical task assessing the mislocalization of tactile stimuli. Co-activation was applied to the index, middle and ring fingers of the right hand either synchronously or asynchronously. Cortical representations for synchronously co-activated fingers moved closer together, whereas cortical representations for asynchronously co-activated fingers became segregated. Behaviorally, this pattern coincided with an increased and reduced number of mislocalizations between synchronously and asynchronously co-activated fingers, respectively. Thus, both synchronous and asynchronous coupling of passive tactile stimulation is able to induce short-term cortical reorganization associated with functionally relevant changes.
Peroxide detoxification by brain cells
2004-11-30

Abstract Peroxides are generated continuously in cells that consume oxygen. Among the different peroxides, hydrogen peroxide is the molecule that is formed in highest quantities. In addition, organic hydroperoxides are synthesized as products of cellular metabolism. Generation and disposal of peroxides is a very important process in the human brain, because cells of this organ consume 20% of the oxygen used by the body. To prevent cellular accumulation of peroxides and damage generated by peroxide‐derived radicals, brain cells contain efficient antioxidative defense mechanisms that dispose of peroxides and protect against oxidative damage. Cultured brain cells have been used frequently to investigate peroxide metabolism of neural cells. Efficient disposal of exogenous hydrogen peroxide was found for cultured astrocytes, oligodendrocytes, microglial cells, and neurons. Comparison of specific peroxide clearance rates revealed that cultured oligodendrocytes dispose of the peroxide quicker than the other neural cell cultures. Both catalase and the glutathione system contribute to the clearance of hydrogen peroxide by brain cells. For efficient glutathione‐dependent reduction of peroxides, neural cells contain glutathione in high concentration and have substantial activity of glutathione peroxidase, glutathione reductase, and enzymes that supply the NADPH required for the glutathione reductase reaction. This article gives an overview on the mechanisms involved in peroxide detoxification in brain cells and on the capacity of the different types of neural cells to dispose of peroxides. © 2004 Wiley‐Liss, Inc.
The matrix-isolated molecular complexes CO/XF (X=Cl,Br,I) and the molecular structure of FC(O)Br
2004-11-30

FC(O)Br has been synthesized, and its IR spectrum in the gas phase and isolated in an Ar matrix, as well as, its Raman spectrum in the solid state at −196 °C has been analyzed. Its molecular structure has been determined and its UV has been measured. FC(O)Br and FC(O)Cl has been photodissociated in an argon matrix at 17 K with a 193 nm laser. The photolysis produces CO and XF which recombine to form CO/XF complexes. The formation of complexes are followed by the shift of the normal vibration modes with respect to CO and XF isolated in argon matrix. In the case of FC(O)Br, three isomers are identified, OC⋯BrF, OC⋯FBr, and CO⋯BrF, whereas for FC(O)Cl only one isomer is observed, OC⋯ClF. High level quantum chemical calculations are used to help the assignment of the different isomers.
The Role of Δ1-Pyrroline-5-Carboxylate Dehydrogenase in Proline Degradation[W]
2004-12-01

Abstract In response to stress, plants accumulate Pro, requiring degradation after release from adverse conditions. Δ1-Pyrroline-5-carboxylate dehydrogenase (P5CDH), the second enzyme for Pro degradation, is encoded by a single gene expressed ubiquitously. To study the physiological function of P5CDH, T-DNA insertion mutants in AtP5CDH were isolated and characterized. Although Pro degradation was undetectable in p5cdh mutants, neither increased Pro levels nor an altered growth phenotype were observed under normal conditions. Thus AtP5CDH is essential for Pro degradation but not required for vegetative plant growth. External Pro application caused programmed cell death, with callose deposition, reactive oxygen species production, and DNA laddering, involving a salicylic acid signal transduction pathway. p5cdh mutants were hypersensitive toward Pro and other molecules producing P5C, such as Arg and Orn. Pro levels were the same in the wild type and mutants, but P5C was detectable only in p5cdh mutants, indicating that P5C accumulation may be the cause for Pro hypersensitivity. Accordingly, overexpression of AtP5CDH resulted in decreased sensitivity to externally supplied Pro. Thus, Pro and P5C/Glu semialdehyde may serve as a link between stress responses and cell death.
Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells
2004-12-01

Obesity-linked insulin resistance is associated with chronic inflammation and cardiovascular complications. Free fatty acids (FFAs) are prominent candidates for the molecular link between these disorders. In this study, we determined whether FFAs contribute to vascular inflammation via induction of interleukin (IL)-6 in coronary artery endothelial cells (CAECs) and coronary artery smooth muscle cells (CASMCs) and whether this is reflected in vivo. In contrast to our findings regarding IL-6 and gp130 (the glycoprotein of 130 kDa) expression, IL-6 receptor mRNA expression was very low in these cells. Palmitate, but not linoleate, induced a significant increase in IL-6 mRNA expression in CAECs (P &amp;lt; 0.001) and, to a less relevant extent, in CASMCs (P &amp;lt; 0.01). gp130 remained unaffected. As to potency, palmitate was comparable with the IL-6−inducer IL-1β. To substantiate our in vitro data, we examined the plasma FFA pattern in 54 healthy human subjects and studied the relation of individual FFAs with plasma IL-6. IL-6 levels correlated with palmitate, but not with other abundant FFAs, even after adjusting for body fat (r = 0.33, P &amp;lt; 0.05) and total FFAs (r = 0.29, P &amp;lt; 0.05). We show here that the common plasma FFA palmitate induces high levels of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This points to a potential contribution of palmitate to vascular inflammation.
Influence of social support and emotional context on pain processing and magnetic brain responses in fibromyalgia
2004-12-01

Abstract Objective To examine the effects of social support provided by the presence of patient's significant other on pain ratings, pain thresholds, and brain activity associated with tactile stimulation in 18 fibromyalgia (FM) patients and 18 migraine patients (controls), and to assess the influence of emotional context on thermal pain perception and processing of non–pain‐related information. Methods Thermal pain thresholds and somatosensory brain magnetic responses elicited by tactile stimulation at the elbow (a painful tender point in the FM group) and at the finger (nonpainful site) were evaluated under 2 experimental conditions of social support: patient alone and patient's significant other present. Brain activity was recorded using a 151‐channel whole‐head magnetoencephalography system. Additionally, the emotional context during presentation of tactile stimuli was manipulated by presenting aversive, pain‐related pictures and neutral pictures and asking the patients to imagine that they were experiencing the situations depicted. Results Thermal pain thresholds indicated greater sensitivity in FM patients than in migraine patients, as well as enhanced sensitivity at the elbow than at the fingers. Specifically, in FM patients, there were significant reductions in pain sensitivity and subjective pain ratings when patients were stimulated at the painful tender point in the presence of their significant others as compared with the ratings when the patients were alone. Brain activity elicited by elbow stimulation was also significantly reduced in FM patients when a significant other was present as compared with the activity when the patient was alone. These effects were not observed in the migraine patients. Conclusion When the significant other was present, FM patients reported less pain and thermal pain sensitivity and showed diminished brain activity elicited upon tactile stimulation of a tender point compared with these levels when the patients were alone. These findings are consistent with the hypothesis that social support through the presence of a significant other can influence pain processing at the subjective–behavioral level as well as the central nervous system level.
Quantum simulation of cosmic inflation in two-component Bose-Einstein condensates
2004-12-01

Generalizing the one-component case, we demonstrate that the propagation of\\nsound waves in two-component Bose-Einstein condensates can also be described in\\nterms of effective sonic geometries under appropriate conditions. In comparison\\nwith the one-component case, the two-component setup offers more flexibility\\nand several advantages. In view of these advantages, we propose an experiment\\nin which the evolution of the inflaton field, and thereby the generation of\\ndensity quantum fluctuations in the very early stages of our universe during\\ninflation, can be simulated, realizing a {\\\\em quantum simulation via analogue\\ngravity models}.\\n
Electroconvulsive Therapy Dosage in Continuation/Maintenance Electroconvulsive Therapy: When Is a New Threshold Titration Necessary?
2004-12-01

Treatment effects and side effects of electroconvulsive therapy (ECT) depend on the level of applied energy in relation to the individual patient's seizure threshold. The threshold is known to increase during a course of frequently repeated ECT treatments and to return to baseline 6 months after cessation of treatment. In continuation ECT, however, as well as after early relapses, the interval between treatments is often longer than a few days but shorter than 6 months. Seizure thresholds for such cases have not been examined. We retrospectively examined 19 patients who had undergone repeated ECT treatments that had been separated by intervals of at least 14 days. We found significant changes in seizure duration, as measured by EEG and the cuff technique, when treatments were separated by durations exceeding 60 days. This is compatible with a decrease in seizure threshold or a loss of anticonvulsant action after 2 months and indicates the necessity to retitrate seizure threshold after this time.