julilili42/papers huggingface dataset:
The CIMT-monitoring panel: a two-step approach to harmonize the enumeration of antigen-specific CD8+ T lymphocytes by structural and functional assays
2007-08-24

The interpretation of the results obtained from immunomonitoring of clinical trials is a difficult task due to the variety of methods and protocols available to detect vaccine-specific T-cell responses. This heterogeneity as well as the lack of standards has led to significant scepticism towards published results. In February 2005, a working group was therefore founded under the aegis of the Association for Immunotherapy of Cancer ("CIMT") in order to compare techniques and protocols applied for the enumeration of antigen-specific T-cell responses. Here we present the results from two consecutive phases of an international inter-laboratory testing project referred to as the "CIMT monitoring panel". A total of 13 centers from six European countries participated in the study in which pre-tested PBMC samples, synthetic peptides and PE-conjugated HLA-tetramers were prepared centrally and distributed to participants. All were asked to determine the number of antigen-specific T-cells in each sample using tetramer staining and one functional assay. The results of the first testing round revealed that the total number of cells analyzed was the most important determinant for the sensitive detection of antigen-specific CD8(+) T-cells by tetramer staining. Analysis by ELISPOT was influenced by a combination of cell number and a resting phase after thawing of peripheral blood mononuclear cells. Therefore, the experiments were repeated in a second phase but now the participants were asked to change their protocols according to the new guidelines distilled from the results of the first phase. The recommendations improved the number of antigen-specific T-cell responses that were detected and decreased the variability between the laboratories. We conclude that a two-step approach in inter-laboratory testing allows the identification of distinct variables that influence the sensitivity of different T-cell assays and to formally show that a defined correction to the protocols successfully increases the sensitivity and reduces the inter-center variability. Such "two-step" inter-laboratory projects could define rational bases for accepted international guidelines and thereby lead to the harmonization of the techniques used for immune monitoring.
The application of Tet repressor in prokaryotic gene regulation and expression
2007-08-24

Summary Inducible gene expression based upon Tet repressor ( tet regulation) is a broadly applied tool in molecular genetics. In its original environment, Tet repressor (TetR) negatively controls tetracycline (tc) resistance in bacteria. In the presence of tc, TetR is induced and detaches from its cognate DNA sequence tetO , so that a tc antiporter protein is expressed. In this article, we provide a comprehensive overview about tet regulation in bacteria and illustrate the parameters of different regulatory architectures. While some of these set‐ups rely on natural tet ‐control regions like those found on transposon Tn 10 , highly efficient variations of this system have recently been adapted to different Gram‐negative and Gram‐positive bacteria. Novel tet ‐controllable artificial or hybrid promoters were employed for target gene expression. They are controlled by regulators expressed at different levels either in a constitutive or in an autoregulated manner. The resulting tet systems have been used for various purposes. We discuss integrative elements vested with tc‐sensitive promoters, as well as tet regulation in Gram‐negative and Gram‐positive bacteria for analytical purposes and for protein overproduction. Also the use of TetR as an in vivo biosensor for tetracyclines or as a regulatory device in synthetic biology constructs is outlined. Technical specifications underlying different regulatory set‐ups are highlighted, and finally recent developments concerning variations of TetR are presented, which may expand the use of prokaryotic tet systems in the future.
Proteome analysis of chemically induced mouse liver tumors with different genotype
2007-08-24

Abstract Mouse liver tumors frequently harbor mutations in Ha‐ras , B‐raf , or Ctnnb1 (encoding β‐catenin). We conducted a proteome analysis with protein extracts from normal mouse liver and from liver tumors which were induced by a single injection of N ‐nitrosodiethylamine (DEN) as initiator followed by multiple injections of two different polychlorinated biphenyls (PCBs) as tumor promoters, or corn oil as a control. Liver tumors were stratified into two classes: they were either mutated in Ctnnb1 and positive for the marker glutamine synthetase (GS(+)), or they lacked Ctnnb1 mutations and were therefore GS‐negative (GS(–)). Proteome analysis by 2‐DE and MS revealed 98 significantly deregulated proteins, 44 in GS(+) and 54 in GS(–) tumors. Twelve of these proteins showed expression changes in both tumor types, but only seven of them were deregulated in the same direction. Several of the identified enzymes could be assigned to fundamental metabolic or other cellular pathways with characteristically different alterations in GS(+) and GS(–) tumors such as ammonia and amino acid turnover, cellular energy supply, and calcium homeostasis. Our data suggest that GS(+) and GS(–) tumor cells show a completely different biology and use divergent evolutionary strategies to gain a selective advantage over normal hepatocytes.
Microscopic theory of superconductor-constriction-superconductor Josephson junctions in a magnetic field
2007-08-24

Self-consistent solutions of microscopic Eilenberger theory are presented for a two-dimensional model of a superconducting channel with a geometric constriction. Magnetic fields, external ones, as well as those caused by the supercurrents are included and the relevant equations are solved numerically without further assumptions. Results concerning the influence of temperature, geometric parameters, of , and of external magnetic fields on the Andreev bound states in the weak link and on the current-phase relation are presented. We find that the Andreev bound states within the junction obtain peculiar substructure when a finite supercurrent flows. As long as the London penetration depth is comparable to or bigger than the extension of the constriction, the Josephson effect is independent of . Furthermore, the weak link is very insensitive to external magnetic fields. Features restricted to a self-consistent calculation are discussed.
Inhibition of Staphylococcal Biofilm Formation by Nitrite
2007-08-25

ABSTRACT Several environmental stresses have been demonstrated to increase polysaccharide intercellular adhesin (PIA) synthesis and biofilm formation by the human pathogens Staphylococcus aureus and Staphylococcus epidermidis . In this study we characterized an adaptive response of S. aureus SA113 to nitrite-induced stress and show that it involves concomitant impairment of PIA synthesis and biofilm formation. Transcriptional analysis provided evidence that nitrite, either as the endogenous product of respiratory nitrate reduction or after external addition, causes repression of the icaADBC gene cluster, mediated likely by IcaR. Comparative microarray analysis revealed a global change in gene expression during growth in the presence of 5 mM sodium nitrite and indicated a response to oxidative and nitrosative stress. Many nitrite-induced genes are involved in DNA repair, detoxification of reactive oxygen and nitrogen species, and iron homeostasis. Moreover, preformed biofilms could be eradicated by the addition of nitrite, likely the result of the formation of toxic acidified nitrite derivatives. Nitrite-mediated inhibition of S. aureus biofilm formation was abrogated by the addition of nitric oxide (NO) scavengers, suggesting that NO is directly or indirectly involved. Nitrite also repressed biofilm formation of S. epidermidis RP62A.
Comprehensive cDNA study and quantitative transcript analysis of mutantOPA1transcripts containing premature termination codons
2007-08-25

Autosomal dominant optic atrophy (adOA) is most commonly caused by mutations in the OPA1 gene. There is a considerable allelic heterogeneity among adOA-associated OPA1 mutations, however these mutations have mostly been identified and studied only at the genomic DNA level. Here we report the identification of 22 novel OPA1 mutations and their analysis at the cDNA level along with 15 already known OPA1 mutations. We found that 18 of these mutations cause splice defects that involve either skipping of the adjacent exon or the activation of a cryptic splice site. We also observed a reduced level of the mutant transcript in several adOA subjects. Allele-specific quantification of the transcript steady-state level was performed for 13 different OPA1 mutations applying pyrosequencing to a RT-PCR amplified cSNP (c.2109C>T) in OPA1. Using this new assay we could demonstrate that the majority of OPA1 mutations that lead to a premature termination codon (PTC) undergo nonsense-mediated mRNA decay (NMD). Mutant transcript levels were reduced between 1.25- and 2.5-fold and varied between PTC containing mutations, and between subjects. Our results emphasize the value of cDNA analysis in the characterization of OPA1 mutations and further strengthen the model of haploinsufficiency as a major pathomechanism in OPA1-associated adOA.
A comparison of implant-supported, bar- or ball-retained mandibular overdentures: a retrospective clinical, microbiologic, and immunologic study of 10 edentulous patients attending a recall visit.
2007-08-27

Within the limitations of this study, both ball attachments and Dolder bars can be recommended for overdenture retention, with either one showing satisfying clinical, microbiologic, and immunologic findings in the peri-implant tissues after several years of service in healthy recall patients with good oral hygiene habits.
Reactions of Transition Metal Azido Complexes and their Reaction Products
2007-08-27

Abstract Transition metal azido complexes can undergo various reactions of their azido group to yield interesting products. The cleavage of the Na α ‐N β bond and elimination of molecular nitrogen can generate nitrido complexes like MoNCl 3 or WNCl 3 , chloroiminato complexes like Cl 3 VNCl, or phosphoraneiminato complexes like [Cl 4 NbNPPh 3 ] 2 with metal nitrogen multiple bonds. The reductive elimination of the complete azido group on the other hand may produce metal(0) fragments which in case of gold(I) azido complexes can combine to form clusters.
Neuronal population coding of continuous and discrete quantity in the primate posterior parietal cortex
2007-08-28

Quantitative knowledge guides vital decisions in the life of animals and humans alike. The posterior parietal cortex in primates has been implicated in representing abstract quantity, both continuous (extent) and discrete (number of items), supporting the idea of a putative generalized magnitude system in this brain area. Whether or not single neurons encode different types of quantity, or how quantitative information is represented in the neuronal responses, however, is unknown. We show that length and numerosity are encoded by functionally overlapping groups of parietal neurons. Using a statistical classifier, we found that the activity of populations of quantity-selective neurons contained accurate information about continuous and discrete quantity. Unexpectedly, even neurons that were nonselective according to classical spike-count measures conveyed robust categorical information that predicted the monkeys' quantity judgments. Thus, different information-carrying processes of partly intermingled neuronal networks in the parietal lobe seem to encode various forms of abstract quantity.
Formation of tight junction: determinants of homophilic interaction between classic claudins
2007-08-29

Claudins are the critical transmembrane proteins in tight junctions. Claudin‐5, for instance, prevents paracellular permeation of small molecules. However, the molecular interaction mechanism is unknown. Hence, the claudin‐claudin interaction and tight junction strand formation were investigated using systematic single mutations. Claudin‐5 mutants trans‐fected into tight junction‐free cells demonstrated that the extracellular loop 2 is involved in strand formation via trans‐interaction, but not via polymerization, along the plasma membrane of one cell. Three phenotypes were obtained: the tight junction type (wild‐type‐like trans‐ and cis‐interaction; the disjunction type (blocked trans‐interaction); the intracellular type (disturbed folding). Combining site‐directed mutagenesis, live‐cell imaging‐, electron microscopy‐, and molecular modeling data led to an antiparallel homodimer homology model of the loop. These data for the first time explain how two claudins hold onto each other and constrict the paracellular space. The intermolecular interface includes aromatic (F147, Y148, Y158) and hydrophilic (Q156, E159) residues. The aromatic residues form a strong binding core between two loops from opposing cells. Since nearly all these residues are conserved in most claudins, our findings are of general relevance for all classical claudins. On the basis of the data we have established a novel molecular concept for tight junction formation.— Piontek, J., Winkler, L., Wolburg, H., Müller, S. L., Zuleger, N., Piehl, C., Wiesner, B., Krause, G., Blasig, I. E. Formation of tight junction: determinants of homophilic interaction between classic clau‐dins. FASEB J. 22, 146–158 (2008)
Differential Recruitment of the Hippocampus, Medial Prefrontal Cortex, and the Human Motion Complex during Path Integration in Humans
2007-08-29

Path integration, the ability to sense self-motion for keeping track of changes in orientation and position, constitutes a fundamental mechanism of spatial navigation and a keystone for the development of cognitive maps. Whereas animal path integration is predominantly supported by the head-direction, grid, and place cell systems, the neural foundations are not well understood in humans. Here we used functional magnetic resonance imaging and a virtual rendition of a triangle completion paradigm to test whether human path integration recruits a cortical system similar to that of rodents and nonhuman primates. Participants traveled along two legs of a triangle before pointing toward the starting location. In accordance with animal models, stronger right hippocampal activation predicted more accurate updating of the starting location on a trial-by-trial basis. Moreover, between-subjects fluctuations in response consistency were negatively correlated with bilateral hippocampal and medial prefrontal activation, and bilateral recruitment of the human motion complex (hMT+) covaried with individual path integration capability. Given that these effects were absent in a perceptual control task, the present study provides the first evidence that visual path integration is related to the dynamic interplay of self-motion processing in hMT+, higher-level spatial processes in the hippocampus, and spatial working memory in medial prefrontal cortex.
Semiclassical expansion of quantum characteristics for many‐body potential scattering problem
2007-08-29

Abstract In quantum mechanics, systems can be described in phase space in terms of the Wigner function and the star‐product operation. Quantum characteristics, which appear in the Heisenberg picture as the Weyl's symbols of operators of canonical coordinates and momenta, can be used to solve the evolution equations for symbols of other operators acting in the Hilbert space. To any fixed order in the Planck's constant, many‐body potential scattering problem simplifies to a statistical‐mechanical problem of computing an ensemble of quantum characteristics and their derivatives with respect to the initial canonical coordinates and momenta. The reduction to a system of ordinary differential equations pertains rigorously at any fixed order in ħ. We present semiclassical expansion of quantum characteristics for many‐body scattering problem and provide tools for calculation of average values of time‐dependent physical observables and cross sections. The method of quantum characteristics admits the consistent incorporation of specific quantum effects, such as non‐locality and coherence in propagation of particles, into the semiclassical transport models. We formulate the principle of stationary action for quantum Hamilton's equations and give quantum‐mechanical extensions of the Liouville theorem on conservation of the phase‐space volume and the Poincaré theorem on conservation of 2 p ‐forms. The lowest order quantum corrections to the Kepler periodic orbits are constructed. These corrections show the resonance behavior.
Bacteria-derived Peptidoglycans Constitute Pathogen-associated Molecular Patterns Triggering Innate Immunity in Arabidopsis
2007-08-31

Pathogen-associated molecular pattern (PAMP)-triggered immunity constitutes the primary plant immune response that has evolved to recognize invariant structures of microbial surfaces. Here we show that Gram-positive bacteria-derived peptidoglycan (PGN) constitutes a novel PAMP of immune responses in Arabidopsis thaliana. Treatment with PGN from Staphylococcus aureus results in the activation of plant responses, such as medium alkalinization, elevation of cytoplasmic calcium concentrations, nitric oxide, and camalexin production and the post-translational induction of MAPK activities. Microarray analysis performed with RNA prepared from PGN-treated Arabidopsis leaves revealed enhanced transcript levels for 236 genes, many of which are also altered upon administration of flagellin. Comparison of cellular responses after treatment with bacteria-derived PGN and structurally related fungal chitin indicated that both PAMPs are perceived via different perception systems. PGN-mediated immune stimulation in Arabidopsis is based upon recognition of the PGN sugar backbone, while muramyl dipeptide, which is inactive in this plant, triggers immunity-associated responses in animals. PGN adds to the list of PAMPs that induce innate immune programs in both plants and animals. However, we propose that PGN perception systems arose independently in both lineages and are the result of convergent evolution.
Transcriptomic and Proteomic Analyses of Pericycle Cells of the Maize Primary Root
2007-08-31

Each plant cell type expresses a unique transcriptome and proteome at different stages of differentiation dependent on its developmental fate. This study compared gene expression and protein accumulation in cell-cycle-competent primary root pericycle cells of maize (Zea mays) prior to their first division and lateral root initiation. These are the only root cells that maintain the competence to divide after they leave the meristematic zone. Pericycle cells of the inbred line B73 were isolated via laser capture microdissection. Microarray experiments identified 32 genes preferentially expressed in pericycle versus all other root cells that have left the apical meristem; selective subtractive hybridization identified seven genes preferentially expressed in pericycle versus central cylinder cells of the same root region. Transcription and protein synthesis represented the most abundant functional categories among these pericycle-specific genes. Moreover, 701 expressed sequence tags (ESTs) were generated from pericycle and central cylinder cells. Among those, transcripts related to protein synthesis and cell fate were significantly enriched in pericycle versus nonpericycle cells. In addition, 77 EST clusters not previously identified in maize ESTs or genomic databases were identified. Finally, among the most abundant soluble pericycle proteins separated via two-dimensional electrophoresis, 20 proteins were identified via electrospray ionization-tandem mass spectrometry, thus defining a reference dataset of the maize pericycle proteome. Among those, two proteins were preferentially expressed in the pericycle. In summary, these pericycle-specific gene expression experiments define the distinct molecular events during the specification of cell-cycle-competent pericycle cells prior to their first division and demonstrate that pericycle specification and lateral root initiation might be controlled by a different set of genes.
Characterization of bixin by LC‐MS and LC‐NMR
2007-08-31

Abstract An overview upon modern analytical techniques for the isolation, separation, and structural identification of the essential bioactive carotenoid bixin is given. Isolation from biological matrices is performed by matrix solid phase dispersion (MSPD). The extract is separated with shape‐selective C 30 columns. Structural assignment of the separated compounds is done by online LC‐MS and capillary HPLC‐NMR.
Role of the ρ meson in the description of pion electroproduction experiments
2007-08-31

We study the p(e,e' pi+)n reaction in the framework of an effective Lagrangian approach including nucleon, pi and rho meson degrees of freedom and show the importance of the rho-meson t-pole contribution to sigmaT, the transverse part of cross section. We test two different field representations of the rho meson, vector and tensor, and find that the tensor representation of the rho meson is more reliable in the description of the existing data. In particular, we show that the rho-meson t-pole contribution, including the interference with an effective non-local contact term, sufficiently improves the description of the recent JLab data at invariant mass W less 2.2 GeV and Q2 less 2.5 GeV2/c2. A ``soft'' variant of the strong piNN and rhoNN form factors is also found to be compatible with these data. On the basis of the successful description of both the sigmaL and sigmaT parts of the cross section we discuss the importance of taking into account the sigmaT data when extracting the charge pion form factor Fpi from sigmaL.
The Paneth Cell α-Defensin Deficiency of Ileal Crohn’s Disease Is Linked to Wnt/Tcf-4
2007-09-01

Abstract Ileal Crohn′s disease (CD), a chronic mucosal inflammation, is characterized by two pertinent features: a specific decrease of Paneth cell-produced antimicrobial α-defensins and the presence of mucosal-adherent bacteria. A mutation in NOD2, the muramyl dipeptide recognition receptor, is found in some patients, which leads to an even more pronounced α-defensin decrease. However, the underlying mechanism remains unclear for the majority of patients. In this study, we report a reduced expression in ileal CD of the Wnt-signaling pathway transcription factor Tcf-4, a known regulator of Paneth cell differentiation and α-defensin expression. Within specimens, the levels of Tcf-4 mRNA showed a high degree of correlation with both HD5 and HD6 mRNA. The levels of Tcf-4 mRNA were decreased in patients with ileal disease irrespective of degree of inflammation, but were not decreased in colonic CD or ulcerative colitis. As a functional indicator of Tcf-4 protein, quantitative binding analysis with nuclear extracts from small intestine biopsies to a Tcf-4 high-affinity binding site in the HD-5 and HD-6 promoters showed significantly reduced activity in ileal CD. Furthermore, a causal link was shown in a murine Tcf-4 knockout model, where the comparably reduced expression of Tcf-4 in heterozygous (+/−) mice was sufficient to cause a significant decrease of both Paneth cell α-defensin levels and bacterial killing activity. Finally, the association between Paneth cell α-defensins and Tcf-4 was found to be independent of the NOD2 genotype. This new link established between a human inflammatory bowel disease and the Wnt pathway/Tcf-4 provides a novel mechanism for pathogenesis in patients with ileal CD.