julilili42/papers huggingface dataset:
Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with IκBα induction and block of NFκB and iNOS activation
2003-12-11

Abstract Inflammation has been implicated in the pathogenesis of Parkinson's disease (PD). In the chronic 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) model of PD, inducible NO synthase (iNOS) derived nitric oxide (NO) is an important mediator of dopaminergic cell death. Ligands of the peroxisome proliferator‐activated receptor (PPAR) exert anti‐inflammatory effects. We here investigated whether pioglitazone, a PPARγ agonist, protected mice from MPTP‐induced dopaminergic cell loss, glial activation, and loss of catecholamines in the striatum. As shown by western blot, PPARγ was expressed in the striatum and the substantia nigra of vehicle‐ and MPTP‐treated mice. Oral administration of 20 mg/(kg day) of pioglitazone protected tyrosine hydroxylase (TH)‐positive substantia nigra neurons from death induced by 5 × 30 mg/kg MPTP. However, the decrease of dopamine in the striatum was only partially prevented. In mice treated with pioglitazone, there were a reduced activation of microglia, reduced induction of iNOS‐positive cells and less glial fibrillary acidic protein positive cells in both striatum and substantia nigra pars compacta. In addition, treatment with pioglitazone almost completely blocked staining of TH‐positive neurons for nitrotyrosine, a marker of NO‐mediated cell damage. Because an increase in inhibitory protein‐κ‐Bα (IκBα) expression and inhibition of translocation of the nuclear factor kappaB (NFκB) subunit p65 to the nucleus in dopaminergic neurons, glial cells and astrocytes correlated with the protective effects of pioglitazone, our results suggest that pioglitazone sequentially acts through PPARγ activation, IκBα induction, block of NFκB activation, iNOS induction and NO‐mediated toxicity. In conclusion, treatment with pioglitazone may offer a treatment opportunity in PD to slow the progression of disease that is mediated by inflammation.
Towards standard testbeds for numerical relativity
2003-12-11

In recent years, many different numerical evolution schemes for Einstein's\\nequations have been proposed to address stability and accuracy problems that\\nhave plagued the numerical relativity community for decades. Some of these\\napproaches have been tested on different spacetimes, and conclusions have been\\ndrawn based on these tests. However, differences in results originate from many\\nsources, including not only formulations of the equations, but also gauges,\\nboundary conditions, numerical methods, and so on. We propose to build up a\\nsuite of standardized testbeds for comparing approaches to the numerical\\nevolution of Einstein's equations that are designed to both probe their\\nstrengths and weaknesses and to separate out different effects, and their\\ncauses, seen in the results. We discuss general design principles of suitable\\ntestbeds, and we present an initial round of simple tests with periodic\\nboundary conditions. This is a pivotal first step toward building a suite of\\ntestbeds to serve the numerical relativists and researchers from related fields\\nwho wish to assess the capabilities of numerical relativity codes. We present\\nsome examples of how these tests can be quite effective in revealing various\\nlimitations of different approaches, and illustrating their differences. The\\ntests are presently limited to vacuum spacetimes, can be run on modest\\ncomputational resources, and can be used with many different approaches used in\\nthe relativity community.\\n
Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors
2003-12-11

Summary Positive selected haematopoietic stem cells are increasingly used for allogeneic transplantation with the CD34 antigen employed in most separation techniques. However, the recently described pentaspan molecule CD133 appears to be a marker of more primitive haematopoietic progenitors. Here we report our experience with a new CD133‐based selection method in 10 paediatric patients with matched unrelated ( n = 2) or mismatched‐related donors ( n = 8). These patients received a combination of stem cells (median = 29·3 × 10 6 /kg), selected with either anti‐CD34 or anti‐CD133 coated microbeads. The proportion of CD133 + selected cells was gradually increased from patient to patient from 10% to 100%. Comparison of CD133 + and CD34 + separation procedures revealed similar purity and recovery of target populations but a lower depletion of T cells by CD133 + selection (3·7 log vs. 4·1 log, P &lt; 0·001). Both separation procedures produced &gt;90% CD34 + /CD133 + double positive target cells. Engraftment occurred in all patients (sustained primary, n = 8; after reconditioning, n = 2). No primary acute graft versus host disease (GvHD) ≥ grade II or chronic GvHD was observed. The patients showed a rapid platelet recovery (median time to independence from substitution = 13·5 d), whereas T cell regeneration was variable. Five patients are alive with a median follow‐up of 10 months. Our data demonstrates the feasibility of CD133 + selection for transplantation from alternative donors and encourages further trials with total CD133 + separated grafts.
Fusion to GFP blocks intercellular trafficking of the sucrose transporter SUT1 leading to accumulation in companion cells
2003-12-11

A fusion with GFP prevents targeting of the sucrose transporter SUT1 to the SE while leading to accumulation in the CC. The 3'-UTR of SUT1 is insufficient for mobilization of either the fusion or GFP alone. It is conceivable that SUT1-GFP protein transport through PD to SE was blocked due to the presence of GFP, resulting in retention in CC particles. Alternatively, SUT1 mRNA transport through the PD could have been blocked due to insertion of GFP between the SUT1 coding sequence and 3'-UTR.
Phthalocyaninatoindium(III) Acetylacetonates for Nonlinear Optics
2003-12-11

Abstract The monomeric octaethylhexyl‐ and tetra‐ tert ‐butyl‐substituted phthalocyanines 3 and 12 with axial acetylacetonate as ligands were synthesized and characterized, in order to compare their optical limiting properties with the state‐of‐the‐art molecule [tetra‐( tert ‐butyl)phthalocyaninato]indium chloride ( t Bu) 4 PcInCl ( 1a ) and the phthalocyanines 1b − f . In addition, the trimer 17 was also synthesized (as a mixture of isomers). The synthesis of 3 , 12 and 17 was carried out by refluxing the corresponding metal‐free phthalocyanines, ( t Bu) 4 PcH 2 ( 2 ), (RO) 8 PcH 2 ( 6 ) (R = 2‐ethylhexyl) and the trimer 16 with an excess of In(acac) 3 in DMF. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)
Mice Deficient for the Ets Transcription Factor Elk-1 Show Normal Immune Responses and Mildly Impaired Neuronal Gene Activation
2003-12-12

The transcription factor Elk-1 belongs to the ternary complex factor (TCF) subfamily of Ets proteins. TCFs interact with serum response factor to bind jointly to serum response elements in the promoters of immediate-early genes (IEGs). TCFs mediate the rapid transcriptional response of IEGs to various extracellular stimuli which activate mitogen-activated protein kinase signaling. To investigate physiological functions of Elk-1 in vivo, we generated Elk-1-deficient mice by homologous recombination in embryonic stem cells. These animals were found to be phenotypically indistinguishable from their wild-type littermates. Histological analysis of various tissues failed to reveal any differences between Elk-1 mutant and wild-type mice. Elk-1 deficiency caused no changes in the proteomic displays of brain or spleen extracts. Also, no immunological defects could be detected in mice lacking Elk-1, even upon infection with coxsackievirus B3. In mouse embryonic fibroblasts, Elk-1 was dispensable for c-fos and Egr-1 transcriptional activation upon stimulation with serum, lysophosphatidic acid, or tetradecanoyl phorbol acetate. However, in brains of Elk-1-deficient mice, cortical and hippocampal CA1 expression of c-fos, but not Egr-1 or c-Jun, was markedly reduced 4 h following kainate-induced seizures. This was not accompanied by altered patterns of neuronal apoptosis. Collectively, our data indicate that Elk-1 is essential neither for mouse development nor for adult life, suggesting compensatory activities by other TCFs.
Modeling of the Optical Properties of Cofacial Chromophore Pairs:  Stilbenophane
2003-12-12

Using electronic absorption and fluorescence spectroscopic techniques, as well as quantum chemical calculations, we have studied the electronic spectra of thia-bridged stilbenophane (TSP) with close cofacial contact of two trans-stilbene (t-SB) units. Compared to the t-SB monomer, the experimental consequences of the cofacial arrangement are (i) a splitting of the main absorption band with a weakly allowed emitting state, and (ii) a strongly red-shifted, unstructured emission spectrum with long fluorescence decay times. According to the theoretical investigations, the two t-SB units are strongly bent in the electronic ground state (S0), because of repulsive π−π overlap. In the first excited state (S1), the t-SB units become almost planar, because of attractive π*−π* overlap. As a consequence, the symmetry-forbidden S0 ↔ S1 transition couples strongly to interchromophore breathing modes of low frequency (ν1 = 67 cm-1, ν2 = 117 cm-1), yielding structureless spectra with large Stokes shifts. The features of the calculated spectra are in good agreement with the experimental data. The results indicate that strong intermolecular vibronic coupling is also responsible for "excimer-like" emission in organic molecular crystals of cofacially arranged molecules. Furthermore, the different geometries in the S0 and S1 states of TSP give evidence for the mechanism of [2+2]photodimerization of t-SB in solutions.
All-Optical Realization of an Atom Laser
2003-12-12

We demonstrate an atom laser using all-optical techniques. A Bose-Einstein condensate of rubidium atoms is created by direct evaporative cooling in a quasistatic dipole trap realized with a single, tightly focused CO2-laser beam. An applied magnetic field gradient allows the formation of the condensate in a field-insensitive m(F)=0 spin projection only, which suppresses fluctuations of the chemical potential from stray magnetic fields. A collimated and monoenergetic beam of atoms is extracted from the Bose-Einstein condensate by continuously lowering the dipole trapping potential in a controlled way to form a novel type of atom laser.
Active‐site residues and amino acid specificity of the bacterial 4′‐phosphopantothenoylcysteine synthetase CoaB
2003-12-14

In bacteria, coenzyme A is synthesized in five steps from d ‐pantothenate. The Dfp flavoprotein catalyzes the synthesis of the coenzyme A precursor 4′‐phosphopantetheine from 4′‐phosphopantothenate and cysteine using the cofactors CTP and flavine mononucleotide via the phosphopeptide‐like compound 4′‐phosphopantothenoylcysteine. The synthesis of 4′‐phosphopantothenoylcysteine is catalyzed by the C‐terminal CoaB domain of Dfp and occurs via the acyl‐cytidylate intermediate 4′‐phosphopantothenoyl‐CMP in two half reactions. In this new study, the molecular characterization of the CoaB domain is continued. In addition to the recently described residue Asn210, two more active‐site residues, Arg206 and Ala276, were identified and shown to be involved in the second half reaction of the ( R )‐4′‐phospho‐ N ‐pantothenoylcysteine synthetase. The proposed intermediate of the ( R )‐4′‐phospho‐ N ‐pantothenoylcysteine synthetase reaction, 4′‐phosphopantothenoyl‐CMP, was characterized by MALDI‐TOF MS and it was shown that the intermediate is copurified with the mutant His‐CoaB N210H/K proteins. Therefore, His‐CoaB N210H and His‐CoaB N210K will be of interest to elucidate the crystal structure of CoaB complexed with the reaction intermediate. Wild‐type His‐CoaB is not absolutely specific for cysteine and can couple derivatives of cysteine to 4′‐phosphopantothenate. However, no phosphopeptide‐like structure is formed with serine. Molecular characterization of the temperature‐sensitive Escherichia coli dfp‐1 mutant revealed that the residue adjacent to Ala276, Ala275 of the strictly conserved AAVAD(275–279) motif, is exchanged for Thr.
Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5
2003-12-15

Ca2+ ions play a fundamental role in many cellular processes, and the extracellular concentration of Ca2+ is kept under strict control to allow the proper physiological functions to take place. The kidney, small intestine, and bone determine the Ca2+ flux to the extracellular Ca2+ pool in a concerted fashion. Transient receptor potential (TRP) cation channel subfamily V, members 5 and 6 (TRPV5 and TRPV6) have recently been postulated to be the molecular gatekeepers facilitating Ca2+ influx in these tissues and are members of the TRP family, which mediates diverse biological effects ranging from pain perception to male aggression. Genetic ablation of TRPV5 in the mouse allowed us to investigate the function of this novel Ca2+ channel in maintaining the Ca2+ balance. Here, we demonstrate that mice lacking TRPV5 display diminished active Ca2+ reabsorption despite enhanced vitamin D levels, causing severe hypercalciuria. In vivo micropuncture experiments demonstrated that Ca2+ reabsorption was malfunctioning within the early part of the distal convolution, exactly where TRPV5 is localized. In addition, compensatory hyperabsorption of dietary Ca2+ was measured in TRPV5 knockout mice. Furthermore, the knockout mice exhibited significant disturbances in bone structure, including reduced trabecular and cortical bone thickness. These data demonstrate the key function of TRPV5 in active Ca2+ reabsorption and its essential role in the Ca2+ homeostasis.
MICA/NKG2D-mediated immunogene therapy of experimental gliomas.
2003-12-15

The failure of conventional cancer therapy renders glioblastoma an attractive target for immunotherapy. Tumor cells expressing ligands of the activating immunoreceptor NKG2D stimulate tumor immunity mediated by natural killer (NK), gammadelta T, and CD8(+) T cells. We report that human glioma cells express the NKG2D ligands MICA, MICB, and members of the UL16-binding protein family constitutively. However, glioma cells resist NK cell cytolysis because of high MHC class I antigen expression. Plasmid-mediated or adenovirus-mediated overexpression of MICA in glioma cells enhances their sensitivity to NK and T-cell responses in vitro and markedly delays the growth of s.c. and intracerebral LN-229 human glioma cell xenografts in nude mice and of SMA-560 gliomas in syngeneic VMDk mice. Glioma cells forming progressive tumors after implantation of stably MICA-transfected human LN-229 cells lost MICA expression, indicating a strong selection against MICA expression in vivo. Rejection of MICA-expressing SMA-560 cells in VMDk mice resulted in protective immunity to a subsequent challenge with wild-type tumor cells. Finally, the growth of syngeneic intracerebral SMA-560 tumors is inhibited by peripheral vaccination with adenovirus-mediated, MICA-infected irradiated tumor cells, and vaccination results in immune cell activation in the NK and T-cell compartments in vivo. These data commend MICA immunogene therapy as a novel experimental treatment for human malignant gliomas.
Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants
2003-12-16

Abstract Adoptive transfer of cytomegalovirus (CMV)-specific T cells can restore long-lasting, virus-specific immunity and clear CMV viremia in recipients of allogeneic stem cell transplants if CD4+ and CD8+ CMV-specific T cells are detected in the recipient after transfer. Current protocols for generating virus-specific T cells use live virus, require leukapheresis of the donor, and are time consuming. To circumvent these limitations, a clinical-scale protocol was developed to generate CMV-specific T cells by using autologous cellular and serum components derived from a single 500-mL blood draw. CMV-specific T cells were stimulated simultaneously with CMV-specific major histocompatibility complex class I (MHC I)- restricted peptides and CMV antigen. Activated T cells were isolated with the interferon-γ (IFN-γ) secretion assay and expanded for 10 days. In 8 randomly selected, CMV-seropositive donors, 1.34 × 108 combined CD4+ and CD8+ CMV-specific T cells, on average, were generated, as determined by antigen-triggered IFN-γ production. CMV-infected fibroblasts were efficiently lysed by the generated T cells, and CMV-specific CD4+ and CD8+ T cells expanded if they were stimulated with natural processed antigen. On the other hand, CD4+ and CD8+ T cell-mediated alloreactivity of generated CMV-specific T-cell lines was reduced compared with that of the starting population. In conclusion, the culture system developed allowed the rapid generation of allodepleted, highly enriched, combined CD4+ and CD8+ CMV-specific T cells under conditions mimicking good manufacturing practice. (Blood. 2004; 103:3565-3572)
From Birds to Humans
2003-12-16

Pulmonary surfactant is a surface-active mixture of phospholipids and specific proteins that lines the epithelial surfaces of mammalian lungs. In the alveoli, its main function is to reduce surface tension to ensure that these structures can remain open during respiratory cycles of contraction and expansion. However, surfactant is also present in the conducting airways, even though they are relatively rigid and do not need a system capable of rapidly lowering surface tension in response to compression. This has raised the question whether there is a difference in composition and function between airway and alveolar surfactant. Interest in this question has been stimulated further by the recognition that surfactant also has important functions in the immune defenses of the respiratory tract. In this review, we describe differences that have been reported between human airway and alveolar surfactant. In addition, we draw parallels between human airway surfactant and surfactant from the lungs of birds. The latter are tubular and rigid and do not undergo cycles of contraction and expansion, thus more resembling the human conducting airways than alveoli. Using this as a model, we propose a new hypothesis to explain structural and functional differences between human airway and alveolar surfactant. We suggest that the molecular composition of surfactant is adapted to differences in the architecture of pulmonary surfaces and to the dynamics of surface area changes during respiration.
MRI-based volumetric differentiation of sporadic cerebellar ataxia
2003-12-16

The term idiopathic cerebellar ataxia (IDCA) designates a variety of cerebellar syndromes that may present with a purely cerebellar syndrome (IDCA-C) or with additional extracerebellar features (IDCA-P). Multiple system atrophy is also a sporadic neurodegenerative disorder of unknown origin that may cause prominent cerebellar symptoms (MSA-C). The final neuropathological answer to the question whether IDCA-P and MSA-C represent different varieties of one disease or two distinct entities is still lacking. Three-dimensional MRI-based volumetry allows morphological investigations intra vitam. Volumetric analysis of cerebellum, brainstem and basal ganglia was therefore performed in 46 patients with sporadic cerebellar ataxia and 16 age-matched healthy controls. Patients with dementia were excluded from the study since cognitive impairment is an exclusion criterion for the diagnosis of MSA. Cerebellar patients were clinically divided into two groups: 33 patients with multiple system atrophy with prominent cerebellar symptoms (MSA-C) and 13 patients with extracerebellar features not corresponding to MSA-C (IDCA-P). There was evidence for substantial cerebellar atrophy in both cerebellar groups while additional brainstem atrophy was significantly more pronounced in MSA-C patients. Absolute caudate and putamen atrophy was found to be restricted to single MSA-C individuals while group comparisons of mean volumes did not yield significant differences from controls. Based on the volumetric data, diagnosis could be correctly predicted in 94% of control, 82% of MSA-C and 100% of IDCA-P individuals. The finding of specific imaging characteristics strengthens (i) the value of MRI volumetry in separating MSA-C from other types of sporadic cerebellar ataxia, and (ii) the hypothesis of two independent neurodegenerative disorders in MSA-C and IDCA-P.
TNFα increases activity of γ‐glutamyl transpeptidase in cultured rat astroglial cells
2003-12-16

Abstract To investigate the presence of γ‐glutamyl transpeptidase (γGT) in brain cells, cultures enriched for astroglial cells, neurons, oligodendroglial cells, and microglial cells were studied. Astroglial cultures contained a specific γGT activity of 2.3 ± 0.9 nmol/min/mg protein. A similar specific γGT activity was measured for oligodendroglial cultures, whereas microglial cells and neurons contained less than 30% of the specific γGT activity of astroglial cultures. The activity of γGT in astroglial cultures was elevated strongly by the presence of tumor necrosis factor‐α (TNFα) in a time‐ and concentration‐dependent manner. Maximal activity of γGT was observed after incubation of astroglial cultures for 3 days with 30 ng/mL TNFα. Under these conditions the specific γGT activity was increased by threefold compared to controls. Presence of the γGT‐inhibitor acivicin completely inhibited γGT activity both in TNFα‐treated and in control cells. In addition, the increase in astroglial γGT activity after application of TNFα was prevented completely by the presence of the protein synthesis inhibitor cycloheximide. γGT is involved in extracellular processing of glutathione (GSH) that is exported by astroglial cells. After TNFα‐treatment the concentration of GSH in the medium of astroglial cells was reduced significantly compared to control cells. In conclusion, the data presented demonstrate that TNFα stimulates γGT synthesis in astroglial cells and thereby improves the capacity to process GSH exported by these cells. © 2003 Wiley‐Liss, Inc.
Recognition of affective prosody: Continuous wavelet measures of event‐related brain potentials to emotional exclamations
2003-12-17

Abstract The affective state of a speaker can be identified from the prosody of his or her speech. Voice quality is the most important prosodic cue for emotion recognition from short verbal utterances and nonverbal exclamations, the latter conveying pure emotion, void of all semantic meaning. We adopted two context violation paradigms—oddball and priming—to study the event‐related brain potentials (ERP) reflecting this recognition process. We found a negative wave, the N300, in the ERPs to contextually incongruous exclamations, and interpreted this component as analogous to the well‐known N400 response to semantically inappropriate words. The N300 appears to be a real‐time psychophysiological measure of spontaneous emotion recognition from vocal cues, which could prove a useful tool for the examination of affective‐prosody comprehension. In addition, we developed a new ERP component detection and estimation method that is based on the continuous wavelet transform (CWT), does not rely on visual inspection of the waveforms, and yields larger statistical difference effects than classical methods.
Nuclear symmetry energy and the neutron skin in neutron-rich nuclei
2003-12-17

The symmetry energy for nuclear matter and its relation to the neutron. skin in finite nuclei is discussed. The symmetry energy as a function of density obtained in a self-consistent Green function approach is presented and compared to the results of other recent theoretical approaches. A partial explanation of the linear relation between the symmetry energy and the neutron skin is proposed. The potential of several experimental methods to extract the neutron skin is examined.