julilili42/papers huggingface dataset:
Bacterial Resistance to Antimicrobial Host Defenses - An Emerging Target for Novel Antiinfective Strategies?
2003-11-01

Increasing bacterial resistance to virtually all available antibiotics causes an urgent need for new antimicrobial drugs, drug targets and therapeutic concepts. This review focuses on strategies to render bacteria highly susceptible to the antimicrobial arsenal of the immune system by targeting bacterial immune escape mechanisms that are conserved in a major number of pathogens. Virtually all innate molecules that inactivate bacteria, ranging from antimicrobial peptides such as defensins and cathelicidins to bacteriolytic enzymes such as lysozyme and group IIA phospholipase A2, are highly cationic in order to facilitate binding to the anionic bacterial cell envelopes. Bacteria have found ways to modulate their anionic cell wall polymers such as peptidoglycan, lipopolysaccharide, teichoic acid or phospholipids by introducing positively charged groups. Two of these mechanisms involving the transfer of D-alanine into teichoic acids and of L-lysine into phospholipids, respectively, have been identified and characterized in Staphylococcus aureus, a major human pathogen in community- and hospital-acquired infections. Inactivation of the responsible genes, dltABCD for alanylation of teichoic acids and mprF for lysinylation of phosphatidylglycerol, renders S. aureus highly susceptible to many human antimicrobial molecules and leads to profoundly attenuated virulence in several animal models. dltABCD- and mprF-related genes are found in the genomes of many bacterial pathogens indicating that the escape from human host defenses by modulation of the cell envelope is a general trait in pathogenic bacteria. This review suggests that inhibitors of DltABCD or MprF should have great potential in complementing or replacing the conventional antibiotic therapies.
Phylogenetic relationships of EuropeanPhlegmaciumspecies (Cortinarius, Agaricales)
2003-11-01

Phylogenetic relationships of 54 European Phlegmacium species, including members of most of the sections of classical systematics, were studied, integrating macro-, micromorphological and chemical characters of the basidiomes, as well as molecular phylogenetic analysis of nuclear rDNA sequences. Microscopical structures of the basidiomes were studied by light microscopy. Basidiospore morphology was examined by scanning electron microscopy. Internal-transcribed spacers (ITS 1 and 2, including the 5.8S) and the D1/D2 (LSU) regions of nuclear rDNA were sequenced and analyzed with a Bayesian Markov chain Monte Carlo approach. Many subgroups detected by the molecular analysis are related to groups known from classical systematical concepts. Among others, these subgroups were significantly supported: i) a group containing most of the members of section Fulvi ss. Brandrud and the species Cortinarius arcuatorum, C. dibaphus and C. multiformis; ii) a group comprising taxa of section Calochroi ss. Brandrud and the species C. fulvocitrinus and C. osmophorus; iii) a group containing species of section Glaucopodes ss. Brandrud and C. caerulescens; iv) a group including members of section Phlegmacioides ss. Brandrud; v) a group that includes the species C. cephalixus, C. nanceiensis and C. mussivus. Stipe shape, color of flesh, pigment contents, KOH reaction on pileipellis and gelatinous layer, degree of development of a gelatinous layer on the pileipellis, and pileipellis structure were useful characters in delimiting subgroups in Phlegmacium, while basidiospore morphology was significant at species level. With the exception of C. glaucopus, C. infractus and C. scaurus, ITS and D1/D2 sequences obtained from collections of the same species from different geographical origins showed very little variation. Our molecular and morphological analyses suggest revisions of the traditional concepts of the subgenus Phlegmacium in Europe.
Volatile Organic Compounds Volatilization from Multicomponent Organic Liquids and Diffusion in Unsaturated Porous Media
2003-11-01

Vapor phase diffusion is an important transport process in the unsaturated zone affecting evaporation of volatile organic compounds (VOCs) from pure and multicomponent organic liquids. To evaluate some widely used empirical relationships for the estimation of effective diffusion coefficients in the unsaturated zone and to assess the validity of Raoult's Law during aging of organic mixtures, two series of laboratory-scale column experiments were performed using pure toluene, pure methyl tert-butyl ether (MTBE), and two multicomponent "kerosene-type" liquids containing four to seven compounds. The analytical one-dimensional solution of Fick's Second Law described the diffusion process of pure compounds very well in two sands with different water contents. The effective diffusion coefficients obtained correspond well to a recently published empirical relationship (Moldrup et al., 2000); the capacity factors fitted indicate equilibrium partitioning of the solute between gas phase and water. A one-dimensional numerical model based on the combination of Fick's Second Law and Raoult's Law was used to predict the volatilization and the diffusion process from multicomponent organic liquids. Both the vapor phase diffusion process of the VOCs and the aging of the organic mixtures were predicted very well solely on the basis of effective diffusion coefficients estimated from the empirical relationship and assuming an ideal mixture (e.g., an activity coefficient of 1 in Raoult's Law).
Template‐free self‐assembling fullerene and lipopeptide conjugates of alamethicin form voltage‐dependent ion channels of remarkable stability and activity
2003-11-01

Abstract N ‐ and C ‐terminally modified with fullerene or lipopeptide alamethicin molecules were designed for the formation of template‐free, self‐assembling, voltage‐dependent ion conducting channels. The automated solid phase synthesis of the alamethicin‐F30 sequence was performed by in situ fluoride activation on 2‐chlorotritylchloride‐polystyrene resin and the conjugation with fullerenes‐C 60 and ‐C 70 was carried out in solution. Voltage‐dependent bilayer experiments revealed preferred channel sizes for C ‐terminal alamethicin F30‐fullerene‐C 60 and ‐C 70 conjugates and higher activity compared with native alamethicin, whereas N ‐terminally linked fullerene balls destabilize pore formation. C ‐terminal alamethicin F30‐fullerene‐C70 conjugates show pore states with remarkably long lifetimes of seconds. C ‐terminal lipopeptide conjugates of alamethicin were prepared by coupling via short peptide spacers with synthetic tripalmitoyl‐S‐glyceryl‐cysteine, which represents the strong membrane anchoring N ‐terminus of bacterial lipoprotein. Alamethicin‐lipopeptide conjugates exhibit high channel forming activities, whereby they self‐assemble and adopt preferred pore states with extremely long lifetimes. The novel membrane modifying peptaibol constructs are valuable lead compounds for developments in sensorics related to transmembrane ion conductance. Copyright © 2003 European Peptide Society and John Wiley &amp; Sons, Ltd.
Survival of a multiple skull trauma: the case of an early neolithic individual from the LBK enclosure at Herxheim (Southwest Germany)
2003-11-01

Abstract The Early Neolithic enclosure of Herxheim yielded the human remains of more than 450 individuals mainly represented by cranial vaults and numerous fractured cranial and postcranial bones. The skulls were shaped post‐mortem into skull caps by intentional separation of the cranial base and facial bones. One of these calottes revealed four ante‐mortem traumatic lesions and additional cut marks.The defects of this individual were analysed in detail to obtain information on the chronology and consequences of the traumata and manipulations and their probable intention. Four marks could be attributed to at least two violent incidents because of their different stages in the healing process. There is no evidence of cranial surgery, but the individual may have received some medical treatment and social care to survive the injuries without complications. The peri‐mortem cut marks and the post‐mortem intentional shaping of the skull cap, however, can be seen as typical for the treatment of the Herxheim dead and cannot be attributed to violent conflicts. The results support the evidence gained from preliminary examinations of the Herxheim human remains and suggest a more complex view of the final phase of the Linear Pottery Culture (LBK) in southwest Germany. Copyright © 2003 John Wiley &amp; Sons, Ltd.
Volatile Organic Compounds Volatilization from Multicomponent Organic Liquids and Diffusion in Unsaturated Porous Media
2003-11-01

Vapor phase diffusion is an important transport process in the unsaturated zone affecting evaporation of volatile organic compounds (VOCs) from pure and multicomponent organic liquids. To evaluate some widely used empirical relationships for the estimation of effective diffusion coefficients in the unsaturated zone and to assess the validity of Raoult's Law during aging of organic mixtures, two series of laboratory‐scale column experiments were performed using pure toluene, pure methyl tert‐butyl ether (MTBE), and two multicomponent “kerosene‐type” liquids containing four to seven compounds. The analytical one‐dimensional solution of Fick's Second Law described the diffusion process of pure compounds very well in two sands with different water contents. The effective diffusion coefficients obtained correspond well to a recently published empirical relationship (Moldrup et al., 2000); the capacity factors fitted indicate equilibrium partitioning of the solute between gas phase and water. A one‐dimensional numerical model based on the combination of Fick's Second Law and Raoult's Law was used to predict the volatilization and the diffusion process from multicomponent organic liquids. Both the vapor phase diffusion process of the VOCs and the aging of the organic mixtures were predicted very well solely on the basis of effective diffusion coefficients estimated from the empirical relationship and assuming an ideal mixture (e.g., an activity coefficient of 1 in Raoult's Law).
Complexity and temporal dynamics of frequency coding in the awake rat auditory cortex
2003-11-01

Abstract Auditory cortical neurons are elements of a neuronal network that decomposes sounds into spectral and temporal information. In particular, their frequency selectivity has been investigated in great detail. Most studies used anaesthetized preparations and found mainly simple V‐shaped tuning. The few data available from awake animals indicate that more complex forms of spectral receptive fields, i.e. frequency response areas, can be found there. We investigated frequency response areas in the awake rat primary auditory cortex using statistical evaluation and found complex forms of frequency response areas with several separate subregions in many neurons, besides classical V‐shaped tuning. Response areas, as determined with narrow band noise, were very similar to those measured with pure tones. Their width was well correlated to the response strength to white noise stimulation. These results suggest that the excitatory subregions of frequency response areas were the neurons' predominant characteristic, relevant also for the processing of more complex types of stimuli. Investigating the spectrotemporal dynamics of frequency response areas revealed that approximately one‐third of the neurons showed long‐lasting excitatory or inhibitory components in addition to the typical ON‐response. Inhibition was usually of longer duration and occurred mainly in frequency ranges outside the range of initial excitatory responses. These results indicate that auditory cortical neurons in awake animals can represent spectrotemporal information of rather different complexity.
Phylogenetic Relationships of European Phlegmacium Species (Cortinarius, Agaricales)
2003-11-01

Phylogenetic relationships of 54 European Phlegmacium species, including members of most of the sections of classical systematics, were studied, integrating macro-, micromorphological and chemical characters of the basidiomes, as well as molecular phylogenetic analysis of nuclear rDNA sequences. Microscopical structures of the basidiomes were studied by light microscopy. Basidiospore morphology was examined by scanning electron microscopy. Internal-transcribed spacers (ITS 1 and 2, including the 5.8S) and the D1/D2 (LSU) regions of nuclear rDNA were sequenced and analyzed with a Bayesian Markov chain Monte Carlo approach. Many subgroups detected by the molecular analysis are related to groups known from classical systematical concepts. Among others, these subgroups were significantly supported: i) a group containing most of the members of section Fulvi ss. Brandrud and the species Cortinarius arcuatorum, C. dibaphus and C. multiformis; ii) a group comprising taxa of section Calochroi ss. Brandrud and the species C. fulvocitrinus and C. osmophorus; iii) a group containing species of section Glaucopodes ss. Brandrud and C. caerulescens; iv) a group including members of section Phlegmacioides ss. Brandrud; v) a group that includes the species C. cephalixus, C. nanceiensis and C. mussivus. Stipe shape, color of flesh, pigment contents, KOH reaction on pileipellis and gelatinous layer, degree of development of a gelatinous layer on the pileipellis, and pileipellis structure were useful characters in delimiting subgroups in Phlegmacium, while basidiospore morphology was significant at species level. With the exception of C. glaucopus, C. infractus and C. scaurus, ITS and D1/D2 sequences obtained from collections of the same species from different geographical origins showed very little variation. Our molecular and morphological analyses suggest revisions of the traditional concepts of the subgenus Phlegmacium in Europe.
Whole Cell Recordings From Respiratory Neurones in an Arterially Perfused in situ Neonatal Rat Preparation
2003-11-01

For synaptic and cellular analyses of the mammalian respiratory network, intracellular recording and good pharmacological access to respiratory neurones is required. Using an existing arterially perfused in situ preparation of neonatal rat, we report on a method allowing stable intracellular recordings of ventrolateral medullary respiratory neurones. The in situ preparation generates a recognizable eupnoeic respiratory motor pattern similar to that reported in vivo. Using this preparation, we have developed a methodology for the use of patch pipettes to record from neurones within the ventral respiratory group. This technique in the arterially perfused neonatal rat is novel and has the advantage that neurones can be recorded from an intact and well‐oxygenated brainstem in which the pontine regions are known to be viable. We describe the methods, present the first whole cell recordings of numerous types of respiratory neurones from neonatal rats in such a preparation, and demonstrate the applicability of the model for neuropharmacological experiments.
Modulation of neuronal activity by the endogenous pentapeptide QYNAD
2003-11-01

Abstract Inflammation and demyelination both contribute to the neurological deficits characteristic of multiple sclerosis. Neurological dysfunctions are attributable to inflammatory demyelination and, in addition, to soluble factors such as nitric oxide, cytokines and antibodies. QYNAD, an endogenous pentapeptide identified in the cerebrospinal fluid of patients with demyelinating disorders, has been proposed to promote axonal dysfunction by blocking sodium channels. The present study aimed at characterizing the properties of QYNAD in acutely isolated thalamic neurons in vitro . QYNAD, but not a scrambled peptide (NYDQA), blocked sodium channels in neurons by shifting the steady‐state inactivation to more negative potentials. Blocking properties followed a dose–response curve with a maximum effect at 10 μ m . A fluorescently labelled QYNAD analogue with retained biological activity specifically stained thalamic neurons, positive for type II sodium channels, thus demonstrating the specificity of QYNAD binding. Our study confirms and extends previous observations describing QYNAD as a potent sodium channel‐blocking agent. These data as well as our preliminary observations in in vivo experiments in an animal model of inflammatory CNS demyelination warrant further in vivo studies in order to clarify the exact pathogenetic role of QYNAD in inflammatory neurological diseases.
Combinatorial Oligocarbamate Collections: Synthesis by the Premix Method and Quality Control by HPLC‐MS
2003-11-01

Abstract The automated solid phase synthesis of 256 complex oligocarbamate collections by the premix method is described. The collections contain up to 1.9×10 6 compounds built up via synthons derived from 18 proteinogenic amino acids. The quality of the collections is investigated by comparing HPLC and electrospray ionization MS data of the products of the premix synthesis to those of a mixture of individually synthesized single compounds. The premix synthesis was found to yield compound mixtures in qualities sufficient for primary screening assays. For highly complex collections, where the determination of each single compound becomes impossible, the signal patterns of electrospray ionization mass spectrometry were compared to simulated mass distributions and good correlations between theoretical and measured data were observed. Therefore, highly diverse and complex oligocarbamate subcollections and individual compounds are conveniently accessible by optimized and reproducible protocols. The compounds are of particular value for lead finding due to their protease resistance and higher lipophilicity compared to peptides.
Clinical Aspects for the Use of DNA Image Cytometry in Detection of Bladder Cancer: A Valuable Tool?
2003-11-01

The employment of DNA flow or image cytometry for oncological diagnostic procedures is favored because of its high correlation to tumor biological behavior. Prognostic statements and therapeutic strategies therefore are based on the high validity of DNA cytometric measurements. Using 151 bladder washings from patients suspected of bladder cancer for this study, we examined the clinical value of various common methods of DNA single cell (SCI) and stemline interpretations (SLI). Comparing the specificity and sensitivity of DNA image cytometry in detection of bladder tumors, we found 81 and 52%, respectively, for SCI of Boecking, 84 and 45% for SLI of Boecking, 61 and 58% for SLI of Fu, and 82 and 40% for conventional stemline interpretation. To improve diagnostic and prognostic validity of DNA image cytometry, we designed our own method of interpretation. In consequence, we identified six single DNA parameters out of all recorded measurements that correlated most to histopathological grading (G1-G3). Creating reference values at random and rating by points, we used a cytometric grading system for ranking. In detection of bladder cancer specificity and sensitivity ultimately arrived at almost 70% in application of our method. Thus, by this study, we were able to show that sensitivity of DNA examination can be increased by combining various DNA parameters. Apart from our own scheme, the discrepancy in interpretation of DNA image cytometry does not allow us to recommend this procedure as the only diagnostic in detection of bladder cancer. However, in regard to prognostic statements, particularly tumor biological behavior, DNA image cytometry appears to be useful.
Relationship between T and B Cell Responses to Proinsulin in Human Type 1 Diabetes
2003-11-01

A bstract : In type 1 diabetes, humoral and cell‐mediated responses to insulin and proinsulin are detectable. Autoantibodies to insulin are associated with impending disease in young individuals and are used as predictive markers to determine disease risk. The aim of this study was to investigate whether different cytokine patterns of cellular reactivity to insulin might serve as additional specific markers of disease maturation and might improve disease prediction in individuals at risk. We correlated T and B cell responses to insulin in subjects with increased genetic risk (HLA‐DRB1*04, DQB1*0302) for diabetes with or without islet autoantibodies (Ab+ subjects and controls, respectively) and HLA‐matched patients. Peripheral blood mononuclear cells were stimulated with 15 overlapping proinsulin peptides (16‐mer), and proinflammatory Th1 (IFNγ) and anti‐inflammatory Th2 (IL‐4) cytokines were analyzed. We observed a simultaneous increase in IL‐4 and IFNγ secretion in early islet autoimmunity of Ab+ subjects, but not in insulin‐treated T1D patients. Furthermore, the increase in IL‐4 secretion in Ab+ subjects was associated with insulin autoantibody responses. There was no correlation of either IFNγ or IL‐4 secretion with insulin antibody responses in patients already treated with exogenous insulin. In conclusion, our findings reveal that quantification of cytokine responses to proinsulin in peripheral blood may prove to be a promising specific marker of diabetes progression and could, in addition to insulin autoantibodies, be used in the prediction of type 1 diabetes.
[Assessment of "self and other perception" of parents in family court disputes based on the Giessen Test].
2003-11-01

30 couples were assessed using the Giessen-Test in regard to their self-images and how they were perceived by their partners. All couples were examined in the course of domestic proceedings at the Department of Psychiatry and Psychotherapy in Childhood and Adolescence (University of Tübingen). Differences between self-image and the partners perception as well as self-image and rating of the partner were worked out. The degree of symmetry and correspondence regarding gender positions and the degree of confirmation/negation of the position were pointed out. No sex differences could be found in regard to role attribution. Sings of sex-specific role perception could not be shown amongst the couples being part of the domestic proceedings. Sex-specific differences in regard to the image as perceived by the other parent do not exist any more. The exact complementary role of ones own role-perception is being attributed to the former partner. The role-characteristics attributed to the former partner can be described as dominant, under-controlled, hypomanic, and inaccessible. Family- and psychodynamic aspects of these results are discussed.