julilili42/papers huggingface dataset:
Covariant constituent quark-gluon model for the glueball-quarkonia content of scalar-isoscalar mesons
2005-02-02

We analyze the mixing of the scalar glueball with the scalar-isoscalar quarkonia states above 1 GeV in a non-local covariant constituent approach. Similarities and differences to the point-particle Klein-Gordon limit and to the quantum mechanical case are elaborated. Model predictions for the two-photon decay rates in the covariant mixing scheme are indicated.
Tetra-t-butyl magnesium phthalocyanine on gold: Electronic structure and molecular orientation
2005-02-02

In this work we have investigated the electronic structure and the molecular orientation of (t-Bu)4PcMg (tetra-t-butyl magnesium phthalocyanine) on polycrystalline and single crystalline gold substrates using photoemission spectroscopy and x-ray absorption spectroscopy, and we compare the results to the unsubstituted PcCu (copper phthalocyanine). The C 1s photoemission spectrum is described similar to unsubstituted relatives with an additional component for the aliphatic substituents. The variation of the excitation energy causes distinct differences in the shape of the C 1s spectrum, which is very useful for the analysis of the molecular orientation in the uppermost layer. It is shown that despite of the sterically demanding substituents, ordered sublimed films of (t-Bu)4PcMg are accessible, the orientation of the molecules, however, is different from the orientation of the unsubstituted relatives.
A three base pair gene variation within the distal 5'-flanking region of the interleukin-10 (IL-10) gene is related to the in vitro IL-10 production capacity of lipopolysaccharide-stimulated peripheral blood mononuclear cells.
2005-02-03

Interleukin-10 (IL-10) is an important multifunctional immunmodulator. There is evidence that IL-10 secretion is associated with certain genetic elements of the proximal IL-10 gene 5'-flanking region. The allelic and genotypic comparison of IL-10 expression by lipopolysaccharide (LPS)- stimulated leukocytes (PBMC) with a recently discovered distal "indel" DNA-sequence variation at - 7400 bp revealed significant inter-individual differences in the IL-10 in vitro production capacity. Homozygotes lacking the three base pairs "GGA" (- 7400del) at this gene locus are characterised by high expression of IL-10 with a median of 1690pg/ml (P <or=0.009). The allelic comparison supports this finding (P <or=0.002). Further analysis of the haplotype -7400/- 1087 showed that homozygotes for - 7400del/- 1087G may be classified as very strong IL-10 responders with a median IL-10 secretion of 2378 pg/ml (P <or=0.025). When leukocytes were stimulated in vitro by dibutyryl-cAMP or infected with Epstein-Barr virus no significant inter-individual differences between the - 7400indel alleles or genotypes and the IL-10 in vitro production capacity were observed. Our findings further the understanding of the complexity of IL-10 gene regulation in relation to defined regulatory gene variations.
Intracellular multiplication of Legionella pneumophila depends on host cell amino acid transporter SLC1A5
2005-02-04

Summary The infectious agent of Legionnaires’ disease, Legionella (L) pneumophila , multiplies intracellularly in eukaryotic cells. This study has been performed to explore the nutrient requirements of L. pneumophila during intracellular replication. In human monocytes, bacterial replication rate was reduced by 76% in defined medium lacking l ‐cysteine, l ‐glutamine or l ‐serine. SLC1A5 (hATB 0,+ ), a neutral amino acid transporter, was upregulated in the host cells after infection with L. pneumophila . Inhibition of SLC1A5 by BCH, a competitive inhibitor of amino acid uptake as well as siRNA silencing of the slc1a5 gene blocked intracellular multiplication of L. pneumophila without compromising viability of host cells. These observations suggest that replication of L. pneumophila depends on the function of host cell SLC1A5.
High Prevalence of Viral Genomes and Multiple Viral Infections in the Myocardium of Adults With “Idiopathic” Left Ventricular Dysfunction
2005-02-08

Background— For a long time, enteroviruses have been considered to be the most common cause of acute viral myocarditis (MC), with possible transition from MC to dilated cardiomyopathy (DCM). Recent investigations have shown, however, that other viruses are also frequently encountered in MC patients, suggesting that persistence of various virus species may play a pathogenic role in the transition from MC to DCM. The purpose of this study was to screen endomyocardial biopsies (EMBs) from patients with “idiopathic” DCM for the presence of viral genomes by using polymerase chain reaction (PCR) to assess the frequency of cardiac viral infections that may be involved in the pathogenesis of the disease. Methods and Results— EMBs were obtained for PCR analysis from 245 consecutive patients (median left ventricular ejection fraction, 35.0%; range, 9% to 59%). PCR and reverse transcription–PCR were performed to detect the genomic sequences of enterovirus (EV), adenovirus (ADV), human cytomegalovirus (HCMV), herpes simplex virus, Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), parvovirus B19 (PVB19), and influenza A and B viruses. Myocardial inflammation was assessed by histological and immunohistological analyses. Viral genomes could be amplified from EMBs of 165 (67.4%) of the 245 DCM patients: EV=23 (9.4%), ADV=4 (1.6%), PVB19=126 (51.4%), HHV-6=53 (21.6%), EBV=5 (2.0%), HCMV=2 (0.8%), including n=45 cases (27.3%) with multiple infections. Active or borderline myocarditis according to the Dallas classification did not exist in any case. Lymphocyte and macrophage infiltrates were not significantly different in virus-positive versus virus-negative patients. Conclusions— Viral genomes were frequently detected in EMBs of patients with systolic left ventricular dysfunction. Our data suggest that myocardial persistence of various viruses, often presenting as multiple infections, may play a role in the pathogenesis of DCM far more frequently than suspected so far.
Retroclival ecchordosis physaliphora: MR imaging and review of the literature.
2005-02-08

Because of the benign character of EP and the difficulties in its histopathologic differentiation from chordomas, precise knowledge of the radiologic characteristics of EP is important. On the basis of these five cases and a review of literature, contrast enhancement and the presence of clinical symptoms seem to be highly reliable parameters in the differential diagnosis of intradural chordoma and EP.
Influence of standard haemodialysis treatment on transcription of human serum- and glucocorticoid-inducible kinase SGK1 and taurine transporter TAUT in blood leukocytes
2005-02-08

Standard HD treatment decreases plasma taurine concentration and upregulates leukocyte SGK1 and TAUT transcription. As SGK1 is a potent regulator of ion channels and transporters in nervous system, heart muscle and epithelial cells, the deranged regulation of SGK1 may contribute to acute side effects of HD treatment.
Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease
2005-02-09

Abstract Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT‐15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age‐ and gender‐matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD. © 2004 Movement Disorder Society
Toward Atom Chips
2005-02-10

As a novel approach for turning the peculiar features of quantum mechanics into practical devices, researchers are investigating the use of ultracold atomic clouds above microchips. Such "atom chips" may find use as sensitive probes for gravity, acceleration, rotation, and tiny magnetic forces. In their Perspective, Fortagh and Zimmermann discuss recent advances toward creating atom chips, in which current-carrying conductors in the chips create magnetic microtraps that confine the atomic clouds. Despite some intrinsic limits to the performance of atom chips, existing technologies are capable of producing atom chips, and many possibilities for their construction remain to be explored.
Human Cytomegalovirus Labeled with Green Fluorescent Protein for Live Analysis of Intracellular Particle Movements
2005-02-11

ABSTRACT Human cytomegalovirus (HCMV) replicates in the nuclei of infected cells. Successful replication therefore depends on particle movements between the cell cortex and nucleus during entry and egress. To visualize HCMV particles in living cells, we have generated a recombinant HCMV expressing enhanced green fluorescent protein (EGFP) fused to the C terminus of the capsid-associated tegument protein pUL32 (pp150). The resulting UL32-EGFP-HCMV was analyzed by immunofluorescence, electron microscopy, immunoblotting, confocal microscopy, and time-lapse microscopy to evaluate the growth properties of this virus and the dynamics of particle movements. UL32-EGFP-HCMV replicated similarly to wild-type virus in fibroblast cultures. Green fluorescent virus particles were released from infected cells. The fluorescence stayed associated with particles during viral entry, and fluorescent progeny particles appeared in the nucleus at 44 h after infection. Surprisingly, strict colocalization of pUL32 and the major capsid protein pUL86 within nuclear inclusions indicated that incorporation of pUL32 into nascent HCMV particles occurred simultaneously with or immediately after assembly of the capsid. A slow transport of nuclear particles towards the nuclear margin was demonstrated. Within the cytoplasm, most particles performed irregular short-distance movements, while a smaller fraction of particles performed centripetal and centrifugal long-distance movements. Although numerous particles accumulated in the cytoplasm, release of particles from infected cells was a rare event, consistent with a release rate of about 1 infectious unit per h per cell in HCMV-infected fibroblasts as calculated from single-step growth curves. UL32-EGFP-HCMV will be useful for further investigations into the entry, maturation, and release of this virus.
Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: Modes of ligand binding and dimerization
2005-02-11

In several species, GAF domains, which are widely expressed small-molecule-binding domains that regulate enzyme activity, are known to bind cyclic nucleotides. However, the molecular mechanism by which cyclic nucleotide binding affects enzyme activity is not known for any GAF domain. In the cyanobacterium, Anabaena , the cyaB1 and cyaB2 genes encode adenylyl cyclases that are stimulated by binding of cAMP to their N-terminal GAF domains. Replacement of the tandem GAF-A/B domains in cyaB1 with the mammalian phosphodiesterase 2A GAF-A/B tandem domains allows regulation of the chimeric protein by cGMP, suggesting a highly conserved mechanism of activation. Here, we describe the 1.9-Å crystal structure of the tandem GAF-A/B domains of cyaB2 with bound cAMP and compare it to the previously reported structure of the PDE2A GAF-A/B. Unexpectedly, the cyaB2 GAF-A/B dimer is antiparallel, unlike the parallel dimer of PDE2A. Moreover, there is clear electron density for cAMP in both GAF-A and -B, whereas in PDE2A, cGMP is found only in GAF-B. Phosphate and ribose group contacts are similar to those in PDE2A. However, the purine-binding pockets appear very different from that in PDE2A GAF-B. Differences in the β2–β3 loop suggest that this loop confers much of the ligand specificity in this and perhaps in many other GAF domains. Finally, a conserved asparagine appears to be a new addition to the signature NKFDE motif, and a mechanism for this motif to stabilize the cNMP-binding pocket is proposed.
Clinical Predictors of Transient Ischemic Attack, Stroke, or Death Within 30 Days of Carotid Angioplasty and Stenting
2005-02-11

Background and Purpose— Carotid angioplasty and stenting (CAS) is currently being assessed in the treatment of severe carotid stenosis. However, little data are available concerning patient-related factors affecting the risk of CAS. The purpose of this study was to identify potential clinical risk factors for the development of postprocedural deficits after CAS. Methods— The clinical characteristics of 299 patients (217 men, 82 women; mean age 69±9 years) who underwent CAS for asymptomatic (n=129, 43%) or symptomatic (n=170, 57%) stenoses and the combined 30-day complication rates (any transient ischemic attack [TIA], minor stroke, major stroke, or death) were analyzed with logistic regression analysis. Results— The overall 30-day TIA rate was 3.7%; the minor stroke rate was 5.3%, the major stroke rate was 0.7%, and the death rate was 0.7%. Although patients presenting with a hemispherical TIA or minor stroke had a significantly higher risk than asymptomatic patients (odds ratio [OR] 5.69; 95% confidence interval [CI], 2.03 to 19.57; P &lt;0.001), the complication rates between patients presenting with a retinal TIA and asymptomatic patients was comparable (OR, 1.42; 95% CI, 0.13 to 9.09; P =0.6). Multivariate regression analysis revealed advanced age (OR, 1.06; 95% CI, 1 to 1.11; P &lt;0.05), stroke (OR, 8; 95% CI, 2.6 to 24.4; P &lt;0.01) or hemispherical TIA (OR, 4.7; 95% CI, 1.6 to 13.3) as presenting symptoms as independent clinical predictors of the combined 30-day outcome measures any TIA, stroke, or death. Conclusion— Aside from advanced age and symptom status, the type of presenting event predicts postprocedural complications after CAS. When evaluating the outcome of CAS and comparing this treatment modality to surgery, patients should be stratified according to their presenting event.
The cyanobacterial tandem GAF domains from the cyaB2 adenylyl cyclase signal via both cAMP-binding sites
2005-02-11

The tandem GAF domains from the cyanobacterium Anabaena PCC7120 cyaB2 adenylyl cyclase form an antiparallel dimer with cAMP bound to all four binding sites. cAMP binding causes highly cooperative allosteric enzyme activation (&gt;500-fold; EC 50 = 1 μM; Hill coefficient &gt;2.0). The cyaB2 GAF domains, like those of the cyclic nucleotide phosphodiesterases (PDEs), contain conserved NKFDE motifs that when mutated in the PDEs abrogate cyclic nucleotide binding. We mutated the aspartic acids within this motif in cyaB2 to determine which domains were required for signaling. Constructs containing an Asp/Ala mutation in either GAF domain still showed positive cooperative cAMP stimulation but with reduced Hill coefficients. The cyaB2 GAF domain NKFDE motifs contain inserts of 14 (GAF-A) and 19 (GAF-B) amino acids not present in PDE2 or cyaB1. Constructs having these inserts deleted could still be activated by cAMP (23- to 100-fold) but lost all positive cooperative activation, suggesting that the inserts play an important role in domain interaction and/or stabilization of the cAMP-binding pockets. In the shortened constructs, even those with a single Asp/Ala mutation in the NKFDE motifs could still be activated by cAMP. However, in a double Asp/Ala mutant of the shortened construct, stimulation by cAMP was almost completely lost, and the EC 50 shifted far to the right. Overall, the data suggest that in GAF domains without these inserts, only the canonical lysine:aspartate salt bridge keeps the α4-helix and the α4-β5 linker that close over the cyclic nucleotide properly oriented, thereby stabilizing the binding pocket. The cyaB2 GAF ensemble appears to be an evolutionary intermediate where both GAF domains still participate in allosteric activation by cAMP.
Inhibition of human immunodeficiency virus type-1 (HIV-1) glycoprotein-mediated cell-cell fusion by immunor (IM28)
2005-02-11

Abstract Background Immunor (IM28), an analog of dehydroepiandrosterone (DHEA), inhibits human immunodeficiency virus type-1 (HIV-1) by inhibiting reverse transcriptase. We assessed the ability of IM28 to inhibit the cell-cell fusion mediated by HIV envelope glycoprotein in an in vitro system. For this purpose, we co-cultured TF228.1.16, a T-cell line expressing stably HIV-1 glycoprotein envelopes, with an equal number of 293/CD4+, another T cell line expressing CD4, and with the SupT1 cell line with or without IM28. Results In the absence of IM28, TF228.1.16 fused with 293/CD4+, inducing numerous large syncytia. Syncytia appeared more rapidly when TF228.1.16 was co-cultured with SupT1 cells than when it was co-cultured with the 293/CD4+ cell line. IM28 (1.6 – 45 μg/ml) completely inhibits cell-cell fusion. IM28 also prevented the development of new syncytia in infected cells and protected naive SupT1 cells from HIV-1 infection. Evaluation of 50% inhibitory dose (IC50) of IM28 revealed a decrease in HIV-1 replication with an IC50 of 22 mM and 50% cytotoxicity dose (CC50) as determined on MT2 cells was 75 mM giving a selectivity index of 3.4 Conclusions These findings suggest that IM28 exerts an inhibitory action on the env proteins that mediate cell-cell fusion between infected and healthy cells. They also suggest that IM28 interferes with biochemical processes to stop the progression of existing syncytia. This property may lead to the development of a new class of therapeutic drug.
4-(3-Hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2,5-dihydro-1H-pyrrole-2,5-dione
2005-02-12

The title compound, C20H19NO7, crystallizes in the space group Pna21. X-ray analysis shows the compound has the desired 3′-hydroxy and 4′-methoxy substitution pattern, as in the natural template combretastatin A-4.
The mutation Y1206S increases the affinity of the sulphonylurea receptor SUR2A for glibenclamide and enhances the effects of coexpression with Kir6.2
2005-02-14

ATP‐sensitive K + channels (K ATP channels) are tetradimeric complexes of inwardly rectifying K + channels (Kir6.x) and sulphonylurea receptors (SURs). The SURs SUR2A (cardiac) and SUR2B (smooth muscle) differ only in the last 42 amino acids. In SUR2B, the mutation Y1206S, located at intracellular loop 8, increases the affinity for glibenclamide (GBC) about 10‐fold. Here, we examined whether the mutation Y1206S in SUR2A had effects similar to those in SUR2B. GBC bound to SUR2A with K D =20 n M ; the mutation increased affinity ∼5 ×. In cells, coexpression of SUR2A with Kir6.2 increased the affinity for GBC∼3 ×; with the mutant, the increase was 9 ×. The mutation did not affect the affinity of SUR2A for openers; coexpression with Kir6.2 reduced opener affinity of wild‐type and mutant SUR2A by about 2 ×. The negative allosteric interaction between the opener, P1075, and GBC at wild‐type and mutant SUR2A was markedly affected by the presence of MgATP and by coexpression with Kir6.2. In inside‐out patches, GBC inhibited the wild‐type Kir6.2/SUR2A and 2B channels with IC 50 values of 27 n M ; the mutation shifted the IC 50 values to ∼1 n M . The data show that the mutation Y1206S increased the affinity of SUR2A for GBC and modulated the effects of coexpression. Overall, the changes were similar to those observed with SUR2B(Y1206S), suggesting that the differences in the last 42 carboxy‐terminal amino acids of SUR2A and 2B are of limited influence on the binding of GBC and P1075 to the SUR2 isoforms. British Journal of Pharmacology (2005) 144 , 1078–1088. doi: 10.1038/sj.bjp.0706142
CYTOKINESIS IN HIGHER PLANTS
2005-02-15

Cytokinesis partitions the cytoplasm between two or more nuclei. In higher plants, cytokinesis is initiated by cytoskeleton-assisted targeted delivery of membrane vesicles to the plane of cell division, followed by local membrane fusion to generate tubulo-vesicular networks. This initial phase of cytokinesis is essentially the same in diverse modes of plant cytokinesis whereas the subsequent transformation of the tubulo-vesicular networks into the partitioning membrane may be different between systems. This review focuses on membrane and cytoskeleton dynamics in cell plate a transient membrane compartment that is formed by the fusion of cytokinetic vesicles and eventually matures into the plasma membranes and cross-wall between daughter cells formation and expansion during somatic cytokinesis.
Role-playing for more realistic technical skills training
2005-02-15

Clinical skills are an important and necessary part of clinical competence. Simulation plays an important role in many fields of medical education. Although role-playing is common in communication training, there are no reports about the use of student role-plays in the training of technical clinical skills. This article describes an educational intervention with analysis of pre- and post-intervention self-selected student survey evaluations. After one term of skills training, a thorough evaluation showed that the skills-lab training did not seem very realistic nor was it very demanding for trainees. To create a more realistic training situation and to enhance students' involvement, case studies and role-plays with defined roles for students (i.e. intern, senior consultant) were introduced into half of the sessions. Results of the evaluation in the second term showed that sessions with role-playing were rated significantly higher than sessions without role-playing.
Design And Synthesis of a Novel Potent Myelin Basic Protein Epitope 87−99 Cyclic Analogue:  Enhanced Stability and Biological Properties of Mimics Render Them a Potentially New Class of Immunomodulators
2005-02-15

A cyclic analogue, [cyclo(87-99)MBP(87)(-)(99)], of the human immunodominant MBP(87)(-)(99) epitope, was designed based on ROESY/NMR distance information and modeling data for linear epitope 87-99, taking into account T-cell (Phe(89), Lys(91), Pro(96)) and HLA (His(88), Phe(90), Ile(93)) contact side-chain information. The cyclic analogue was found to induce experimental allergic encephalomyelitis (EAE), to bind HLA-DR4, and to increase CD4 T-cell line proliferation, like that of the conformationally related linear MBP(87)(-)(99) epitope peptide. The mutant cyclic peptides, the cyclo(91-99)[Ala(96)]MBP(87)(-)(99) and the cyclo(87-99)[Arg(91)Ala(96)]MBP(87)(-)(99), reported previously for suppressing, to a varying degree, autoimmune encephalomyelitis in a rat animal model, were found in this study to possess the following immunomodulatory properties: (i) they suppressed the proliferation of a CD4 T-cell line raised from a multiple sclerosis patient, (ii) they scored the best in vitro TH2/TH1 cytokine ratio in peripheral blood mononuclear cell cultures derived from 13 multiple sclerosis patients, inducing IL-10 selectively, and (iii) they bound to HLA-DR4, first to be reported for cyclic MBP peptides. In addition, cyclic peptides were found to be more stable to lysosomal enzymes and Cathepsin B, D, and H, compared to their linear counterparts. Taken together, these data render cyclic mimics as putative drugs for treating multiple sclerosis and potentially other Th1-mediated autoimmune diseases.
Reproduction Number
2005-02-15

Abstract The basic reproduction number (or ratio) is the expected number of secondary cases of an infection, which one typical case could generate during its infectious period in a completely susceptible population. It is the most important theoretical concept in communicable disease epidemiology.