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Showing papers by "University of Würzburg published in 2001"


Journal ArticleDOI
TL;DR: The molecular determinants of Listeria virulence and their mechanism of action are described and the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listersia infection is summarized.
Abstract: The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research.

2,139 citations


Journal ArticleDOI
26 Oct 2001-Science
TL;DR: A large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators are found, consistent with the ability of both species to adapt to diverse environments.
Abstract: Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.

1,430 citations


Journal ArticleDOI
TL;DR: It is proposed that chance evolutionary processes, history, and constraints should be considered and quantifying variance between individuals and populations and using fitness measurements to test the adaptive value of traits identified in insect color vision systems are suggested.
Abstract: We review the physiological, molecular, and neural mechanisms of insect color vision. Phylogenetic and molecular analyses reveal that the basic bauplan, UV-blue-green-trichromacy, appears to date back to the Devonian ancestor of all pterygote insects. There are variations on this theme, however. These concern the number of color receptor types, their differential expression across the retina, and their fine tuning along the wavelength scale. In a few cases (but not in many others), these differences can be linked to visual ecology. Other insects have virtually identical sets of color receptors despite strong differences in lifestyle. Instead of the adaptionism that has dominated visual ecology in the past, we propose that chance evolutionary processes, history, and constraints should be considered. In addition to phylogenetic analyses designed to explore these factors, we suggest quantifying variance between individuals and populations and using fitness measurements to test the adaptive value of traits identified in insect color vision systems.

1,308 citations


Journal ArticleDOI
03 Aug 2001-Science
TL;DR: DM2 is caused by a CCTG expansion located in intron 1 of the zinc finger protein 9 (ZNF9) gene, indicating that microsatellite expansions in RNA can be pathogenic and cause the multisystemic features of DM1 and DM2.
Abstract: Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, can be caused by a mutation on either chromosome 19q13 (DM1) or 3q21 (DM2/PROMM). DM1 is caused by a CTG expansion in the 3' untranslated region of the dystrophia myotonica-protein kinase gene (DMPK). Several mechanisms have been invoked to explain how this mutation, which does not alter the protein-coding portion of a gene, causes the specific constellation of clinical features characteristic of DM. We now report that DM2 is caused by a CCTG expansion (mean approximately 5000 repeats) located in intron 1 of the zinc finger protein 9 (ZNF9) gene. Parallels between these mutations indicate that microsatellite expansions in RNA can be pathogenic and cause the multisystemic features of DM1 and DM2.

1,163 citations


Journal ArticleDOI
21 Sep 2001-Cell
TL;DR: These studies provide one potential explanation for Holt-Oram syndrome conduction system defects, suggest mechanisms for intrafamilial phenotypic variability, and account for related cardiac malformations caused by other transcription factor mutations.

1,007 citations


Journal ArticleDOI
TL;DR: This review will focus preferentially on the role of chemokines duringskin wound healing and intends to provide an update on the multiplefunctions of individual chemokine functions during the phases of woundrepair.
Abstract: Healing of wounds is one of the most complex biological events after birth as a result of the interplay of different tissue structures and a large number of resident and infiltrating cell types. The latter are mainly constituted by leukocyte subsets (neutrophils, macrophages, mast cells, and lymphocytes), which sequentially infiltrate the wound site and serve as immunological effector cells but also as sources of inflammatory and growth-promoting cytokines. Recent data demonstrate that recruitment of leukocyte subtypes is tightly regulated by chemokines. Moreover, the presence of chemokine receptors on resident cells (e.g., keratinocytes, endothelial cells) indicates that chemokines also contribute to the regulation of epithelialization, tissue remodeling, and angiogenesis. Thus, chemokines are in an exclusive position to integrate inflammatory events and reparative processes and are important modulators of human-skin wound healing. This review will focus preferentially on the role of chemokines during skin wound healing and intends to provide an update on the multiple functions of individual chemokines during the phases of wound repair.

924 citations


Journal ArticleDOI
TL;DR: The bulk of water diffuses as single molecules across a lipophilic barrier while a minor fraction travels along polar pores, and the role the plant cuticle plays in ensuring the survival and reproductive success of an individual plant is indicated.
Abstract: The cuticle is the major barrier against uncontrolled water loss from leaves, fruits and other primary parts of higher plants. More than 100 mean values for water permeabilities determined with isolated leaf and fruit cuticles from 61 plant species are compiled and discussed in relation to plant organ, natural habitat and morphology. The maximum barrier properties of plant cuticles exceed that of synthetic polymeric films of equal thickness. Cuticular water permeability is not correlated to the thickness of the cuticle or to wax coverage. Relationships between cuticular permeability, wax composition and physical properties of the cuticle are evaluated. Cuticular permeability to water increases on the average by a factor of 2 when leaf surface temperature is raised from 15 degrees C to 35 degrees C. Organic compounds of anthropogenic and biogenic origin may enhance cuticular permeability. The pathway taken by water across the cuticular transport barrier is reviewed. The conclusion from this discussion is that the bulk of water diffuses as single molecules across a lipophilic barrier while a minor fraction travels along polar pores. Open questions concerning the mechanistic understanding of the plant cuticular transport barrier and the role the plant cuticle plays in ensuring the survival and reproductive success of an individual plant are indicated.

775 citations


Journal ArticleDOI
19 Jan 2001-Science
TL;DR: The electron-hole complex is shown to be equivalent to entangled states of two interacting spins in a pair of vertically aligned, self-assembled quantum dots.
Abstract: We demonstrate coupling and entangling of quantum states in a pair of vertically aligned, self-assembled quantum dots by studying the emission of an interacting electron-hole pair (exciton) in a single dot molecule as a function of the separation between the dots. An interaction-induced energy splitting of the exciton is observed that exceeds 30 millielectron volts for a dot layer separation of 4 nanometers. The results are interpreted by mapping the tunneling of a particle in a double dot to the problem of a single spin. The electron-hole complex is shown to be equivalent to entangled states of two interacting spins.

733 citations


Journal ArticleDOI
TL;DR: In this article, the authors discuss ways in which PAIs contribute to the pathogenic potency of bacteria, and the idea that genetic entities similar to genomic islands may also be present in the genomes of eukaryotes.
Abstract: The compositions of bacterial genomes can be changed rapidly and dramatically through a variety of processes including horizontal gene transfer. This form of change is key to bacterial evolution, as it leads to ‘evolution in quantum leaps’. Horizontal gene transfer entails the incorporation of genetic elements transferred from another organism—perhaps in an earlier generation—directly into the genome, where they form ‘genomic islands’, i.e. blocks of DNA with signatures of mobile genetic elements. Genomic islands whose functions increase bacterial fitness, either directly or indirectly, have most likely been positively selected and can be termed ‘fitness islands’. Fitness islands can be divided into several subtypes: ‘ecological islands’ in environmental bacteria and ‘saprophytic islands’, ‘symbiosis islands’ or ‘pathogenicity islands’ (PAIs) in microorganisms that interact with living hosts. Here we discuss ways in which PAIs contribute to the pathogenic potency of bacteria, and the idea that genetic entities similar to genomic islands may also be present in the genomes of eukaryotes.

604 citations


Journal ArticleDOI
TL;DR: It is shown that infection of cells with influenza A virus leads to biphasic activation of the Raf/MEK/ERK cascade, which seems to be essential for virus production and RNP export from the nucleus during the viral life cycle.
Abstract: Influenza A viruses are important worldwide pathogens in humans and different animal species. The functions of most of the ten different viral proteins of this negative-strand RNA virus have been well elucidated. However, little is known about the virus-induced intracellular signalling events that support viral replication. The Raf/MEK/ERK cascade is the prototype of mitogen-activated protein (MAP) kinase cascades and has an important role in cell growth, differentiation and survival. Investigation of the function of this pathway has been facilitated by the identification of specific inhibitors such as U0126, which blocks the cascade at the level of MAPK/ERK kinase (MEK). Here we show that infection of cells with influenza A virus leads to biphasic activation of the Raf/MEK/ERK cascade. Inhibition of Raf signalling results in nuclear retention of viral ribonucleoprotein complexes (RNPs), impaired function of the nuclear-export protein (NEP/NS2) and concomitant inhibition of virus production. Thus, signalling through the mitogenic cascade seems to be essential for virus production and RNP export from the nucleus during the viral life cycle.

498 citations


Journal ArticleDOI
TL;DR: The serotonin dependence of cocaine reward in DAT knockout mice is confirmed by the elimination of cocaine place preference in Dat/SERT double knockout mice, and insights into the brain molecular targets necessary for cocaine Reward in knockout mice that develop in their absence are provided.
Abstract: Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioral features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement, as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development.

Journal ArticleDOI
TL;DR: A new database of this kind for the Phanerozoic fossil record of marine invertebrates is introduced and four substantially distinct analytical methods that estimate taxonomic diversity by quantifying and correcting for variation through time in the number and nature of inventories are applied.
Abstract: Global diversity curves reflect more than just the number of taxa that have existed through time: they also mirror variation in the nature of the fossil record and the way the record is reported. These sampling effects are best quantified by assembling and analyzing large numbers of locality-specific biotic inventories. Here, we introduce a new database of this kind for the Phanerozoic fossil record of marine invertebrates. We apply four substantially distinct analytical methods that estimate taxonomic diversity by quantifying and correcting for variation through time in the number and nature of inventories. Variation introduced by the use of two dramatically different counting protocols also is explored. We present sampling-standardized diversity estimates for two long intervals that sum to 300 Myr (Middle Ordovician-Carboniferous; Late Jurassic-Paleogene). Our new curves differ considerably from traditional, synoptic curves. For example, some of them imply unexpectedly low late Cretaceous and early Tertiary diversity levels. However, such factors as the current emphasis in the database on North America and Europe still obscure our view of the global history of marine biodiversity. These limitations will be addressed as the database and methods are refined.

Journal ArticleDOI
TL;DR: The proportion of cytomegalovirus reactivation during lactation almost equals maternal seroprevalence, which has been underestimated and may be associated with a symptomatic infection.

Journal ArticleDOI
TL;DR: PDS proved to be a reliable diagnostic method for qualitative grading of the vascularity of the synovial tissue in clinical practice and allows further differentiation of the hypertrophic synovium.
Abstract: Objective To examine the significance of power Doppler sonography (PDS) in the diagnosis of synovial hypertrophy of the knee joint by verifying and comparing the PDS findings with histopathologic findings of synovial membrane vascularity. Methods The knee joints of 23 patients who were undergoing arthroplasty of the knee joint because of osteoarthritis or rheumatoid arthritis were examined with ultrasound before arthroplasty. The vascularity of the synovial membrane was classified semiquantitatively using PDS. A sample of synovial tissue was obtained during the arthroplasty, and the vascularity of the synovial tissue was evaluated by immunohistochemistry (factor VIII) and was graded qualitatively by a pathologist who was unaware of the PDS findings. The visual qualitative grading by the examiner was controlled by analyzing PDS images and histologic samples using a digital image evaluation system. Results The correlation between the qualitative PDS results and the qualitative grading of the vascularity by the pathologist was 0.89 by Spearman's ρ (P < 0.01). The Pearson correlation coefficient between the digital analysis of the PDS images and the digital analysis of the tissue sections was 0.81 (P < 0.01). Digital image analysis and qualitative grading by the examiner had a correlation of 0.89 by Spearman's ρ (P < 0.01) for the PDS images. The correlation between the qualitative estimation of vascularity by the pathologist and the digital image analysis was 0.88 by Spearman's ρ (P < 0.01). Conclusion In the present study, PDS proved to be a reliable diagnostic method for qualitative grading of the vascularity of the synovial tissue. In clinical practice, PDS allows further differentiation of the hypertrophic synovium.

Journal ArticleDOI
01 Jul 2001-Blood
TL;DR: Investigation of 10 patients and their relatives with Fas mutations revealed that all had defective lymphocyte apoptosis and most had other features of ALPS, implicate a role for Fas-mediated apoptosis in preventing B-cell and T-cell lymphomas.

Journal ArticleDOI
TL;DR: Using a positional cloning approach, five different heterozygous loss-of-function mutations in the gene for ɛ-sarcoglycan (SGCE) are identified, which is mapped to a refined critical region of about 3.2 Mb and shows a marked difference in penetrance depending on the parental origin of the disease allele.
Abstract: The dystonias are a common clinically and genetically heterogeneous group of movement disorders More than ten loci for inherited forms of dystonia have been mapped, but only three mutated genes have been identified so far These are DYT1, encoding torsin A and mutant in the early-onset generalized form, GCH1 (formerly known as DYT5), encoding GTP-cyclohydrolase I and mutant in dominant dopa-responsive dystonia, and TH, encoding tyrosine hydroxylase and mutant in the recessive form of the disease Myoclonus-dystonia syndrome (MDS; DYT11) is an autosomal dominant disorder characterized by bilateral, alcohol-sensitive myoclonic jerks involving mainly the arms and axial muscles Dystonia, usually torticollis and/or writer's cramp, occurs in most but not all affected patients and may occasionally be the only symptom of the disease In addition, patients often show prominent psychiatric abnormalities, including panic attacks and obsessive-compulsive behavior In most MDS families, the disease is linked to a locus on chromosome 7q21 (refs 11-13) Using a positional cloning approach, we have identified five different heterozygous loss-of-function mutations in the gene for epsilon-sarcoglycan (SGCE), which we mapped to a refined critical region of about 32 Mb SGCE is expressed in all brain regions examined Pedigree analysis shows a marked difference in penetrance depending on the parental origin of the disease allele This is indicative of a maternal imprinting mechanism, which has been demonstrated in the mouse epsilon-sarcoglycan gene

Journal ArticleDOI
TL;DR: It is shown that screening of genomic sequences is a valuable tool with which to identify novel regulatory peptides in β-defensins, a family of antimicrobial peptides differentially expressed in most tissues, regulated by specific mechanisms, and exerting physiological functions not only related to direct host defense.
Abstract: Previous studies have shown the implication of β-defensins in host defense of the human body. The human β-defensins 1 and 2 (hBD-1, hBD-2) have been isolated by biochemical methods. Here we report the identification of a third human β-defensin, called human β-defensin 3 (hBD-3; cDNA sequence, Genbank accession no. AF295370), based on bioinformatics and functional genomic analysis. Expression of hBD-3 is detected throughout epithelia of many organs and in non-epithelial tissues. In contrast to hBD-2, which is upregulated by microorganisms or tumor necrosis factor-α (TNF-α), hBD-3 expression is increased particularly after stimulation by interferon-γ. Synthetic hBD-3 exhibits a strong antimicrobial activity against gram-negative and gram-positive bacteria and fungi, including Burkholderia cepacia. In addition, hBD-3 activates monocytes and elicits ion channel activity in biomembranes, specifically in oocytes of Xenopus laevis. This paper also shows that screening of genomic sequences is a valuable tool with which to identify novel regulatory peptides. Human β-defensins represent a family of antimicrobial peptides differentially expressed in most tissues, regulated by specific mechanisms, and exerting physiological functions not only related to direct host defense.

Journal ArticleDOI
01 Nov 2001-Nature
TL;DR: Adaptive femtosecond pulse shaping can reveal complex laser fields to achieve chemically selective molecular excitation and the results prove that phase coherences of the solute molecule persist for more than 100 fs in the solvent environment.
Abstract: Coherent light sources can be used to manipulate the outcome of light–matter interactions by exploiting interference phenomena in the time and frequency domain. A powerful tool in this emerging field of ‘quantum control’1,2,3,4,5,6 is the adaptive shaping of femtosecond laser pulses7,8,9,10, resulting, for instance, in selective molecular excitation. The basis of this method is that the quantum system under investigation itself guides an automated search, via iteration loops, for coherent light fields best suited for achieving a control task designed by the experimenter11. The method is therefore ideal for the control of complex experiments7,12,13,14,15,16,17,18,19,20. To date, all demonstrations of this technique on molecular systems have focused on controlling the outcome of photo-induced reactions in identical molecules, and little attention has been paid to selectively controlling mixtures of different molecules. Here we report simultaneous but selective multi-photon excitation of two distinct electronically and structurally complex dye molecules in solution. Despite the failure of single parameter variations (wavelength, intensity, or linear chirp control), adaptive femtosecond pulse shaping can reveal complex laser fields to achieve chemically selective molecular excitation. Furthermore, our results prove that phase coherences of the solute molecule persist for more than 100 fs in the solvent environment.

Journal ArticleDOI
TL;DR: The high recovery of strains with antimicrobial activity suggests that marine sponges represent an ecological niche which harbors a hitherto largely uncharacterized microbial diversity and, concomitantly, a yet untapped metabolic potential.

Journal ArticleDOI
TL;DR: This review focuses on five nonmetal catalytic systems which have attained prominence in the oxidation field in view of their efficacy and their potential for future development; stoichiometric cases have been mentioned to provide overview and scope.
Abstract: Nonmetal oxidation catalysts have gained much attention in recent years. The reason for this surge in activity is 2-fold: On one hand, a number of such catalysts has become readily accessible; on the other hand, such catalysts are quite resistant toward self-oxidation and compatible under aerobic and aqueous reaction conditions. In this review, we have focused on five nonmetal catalytic systems which have attained prominence in the oxidation field in view of their efficacy and their potential for future development; stoichiometric cases have been mentioned to provide overview and scope. Such nonmetal oxidation catalysts include the alpha-halo carbonyl compounds 1, ketones 2, imines 3, iminium salts 4, and nitroxyl radicals 5. In combination with a suitable oxygen source (H2O2, KHSO5, NaOCl), these catalysts serve as precursors to the corresponding oxidants, namely, the perhydrates I, dioxiranes II, oxaziridines III, oxaziridinium ions IV, and finally oxoammonium ions V. A few of the salient features about these nonmetal, catalytic systems shall be reiterated in this summary. The first class entails the alpha-halo ketones, which catalyze the oxidation of a variety of organic substrates [figure: see text] by hydrogen peroxide as the oxygen source. The perhydrates I, formed in situ by the addition of hydrogen peroxide to the alpha-halo ketones, are quite strong electrophilic oxidants and expectedly transfer an oxygen atom to diverse nucleophilic acceptors. Thus, alpha-halo ketones have been successfully employed for catalytic epoxidation, heteroatom (S, N) oxidation, and arene oxidation. Although high diastereoselectivities have been achieved by these nonmetal catalysts, no enantioselective epoxidation and sulfoxidation have so far been reported. Consequently, it is anticipated that catalytic oxidations by perhydrates hold promise for further development, especially, and should ways be found to transfer the oxygen atom enantioselectively. The second class, namely, the dioxiranes, has been extensively used during the last two decades as a convenient oxidant in organic synthesis. These powerful and versatile oxidizing agents are readily available from the appropriate ketones by their treatment [figure: see text] with potassium monoperoxysulfate. The oxidations may be performed either under stoichiometric or catalytic conditions; the latter mode of operation is featured in this review. In this case, a variety of structurally diverse ketones have been shown to catalyze the dioxirane-mediated epoxidation of alkenes by monoperoxysulfate as the oxygen source. By employing chiral ketones, highly enantioselective (up to 99% ee) epoxidations have been developed, of which the sugar-based ketones are so far the most effective. Reports on catalytic oxidations by dioxiranes other than epoxidations are scarce; nevertheless, fructose-derived ketones have been successfully employed as catalysts for the enantioselective CH oxidation in vic diols to afford the corresponding optically active alpha-hydroxy ketones. To date, no catalytic asymmetric sulfoxidations by dioxiranes appear to have been documented in the literature, an area of catalytic dioxirane chemistry that merits attention. A third class is the imines; their reaction with hydrogen peroxide or monoperoxysulfate affords oxaziridines. These relatively weak electrophilic oxidants only manage to oxidize electron-rich substrates such as enolates, silyl enol ethers, sulfides, selenides, and amines; however, the epoxidation of alkenes has been achieved with activated oxaziridines produced from perfluorinated imines. Most of the oxidations by in-situ-generated oxaziridines have been performed stoichiometrically, with the exception of sulfoxidations. When chiral imines are used as catalysts, optically active sulfoxides are obtained in good ee values, a catalytic asymmetric oxidation by oxaziridines that merits further exploration. The fourth class is made up by the iminium ions, which with monoperoxysulfate lead to the corresponding oxaziridinium ions, structurally similar to the above oxaziridine oxidants except they possess a much more strongly electrophilic oxygen atom due to the positively charged ammonium functionality. Thus, oxaziridinium ions effectively execute besides sulfoxidation and amine oxidation the epoxidation of alkenes under catalytic conditions. As expected, chiral iminium salts catalyze asymmetric epoxidations; however, only moderate enantioselectivities have been obtained so far. Although asymmetric sulfoxidation has been achieved by using stoichiometric amounts of isolated optically active oxaziridinium salts, iminium-ion-catalyzed asymmetric sulf-oxidations have not been reported to date, which offers attractive opportunities for further work. The fifth and final class of nonmetal catalysts concerns the stable nitroxyl-radical derivatives such as TEMPO, which react with the common oxidizing agents (sodium hypochlorite, monoperoxysulfate, peracids) to generate oxoammonium ions. The latter are strong oxidants that chemoselectively and efficiently perform the CH oxidation in alcohols to produce carbonyl compounds rather than engage in the transfer of their oxygen atom to the substrate. Consequently, oxoammonium ions behave quite distinctly compared to the previous four classes of oxidants in that their catalytic activity entails formally a dehydrogenation, one of the few effective nonmetal-based catalytic transformations of alcohols to carbonyl products. Since less than 1 mol% of nitroxyl radical is required to catalyze the alcohol oxidation by the inexpensive sodium hypochlorite as primary oxidant under mild reaction conditions, this catalytic process holds much promise for future practical applications.

Journal ArticleDOI
TL;DR: It is concluded that, by regulating the extent of apoplastic barriers and their chemical composition, plants can effectively regulate the uptake or loss of water and solutes.
Abstract: The exodermis (hypodermis with Casparian bands) of plant roots represents a barrier of variable resistance to the radial flow of both water and solutes and may contribute substantially to the overall resistance. The variability is a result largely of changes in structure and anatomy of developing roots. The extent and rate at which apoplastic exodermal barriers (Casparian bands and suberin lamellae) are laid down in radial transverse and tangential walls depends on the response to conditions in a given habitat such as drought, anoxia, salinity, heavy metal or nutrient stresses. As Casparian bands and suberin lamellae form in the exodermis, the permeability to water and solutes is differentially reduced. Apoplastic barriers do not function in an all-or-none fashion. Rather, they exhibit a selectivity pattern which is useful for the plant and provides an adaptive mechanism under given circumstances. This is demonstrated for the apoplastic passage of water which appears to have an unusually high mobility, ions, the apoplastic tracer PTS, and the stress hormone ABA. Results of permeation properties of apoplastic barriers are related to their chemical composition. Depending on the growth regime (e.g. stresses applied) barriers contain aliphatic and aromatic suberin and lignin in different amounts and proportion. It is concluded that, by regulating the extent of apoplastic barriers and their chemical composition, plants can effectively regulate the uptake or loss of water and solutes. Compared with the uptake by root membranes (symplastic and transcellular pathways), which is under metabolic control, this appears to be an additional or compensatory strategy of plants to acquire water and solutes.

Journal ArticleDOI
TL;DR: It is concluded that neuromelanin is the major iron storage in substantia nigra neurones in normal individuals.
Abstract: Information on the molecular distribution and ageing trend of brain iron in post-mortem material from normal subjects is scarce. Because it is known that neuromelanin and ferritin form stable complexes with iron(III), in this study we measured the concentration of iron, ferritin and neuromelanin in substantia nigra from normal subjects, aged between 1 and 90 years, dissected post mortem. Iron levels in substantia nigra were 20 ng/mg in the first year of life, had increased to 200 ng/mg by the fourth decade and remained stable until 90 years of age. The H-ferritin concentration was also very low (29 ng/mg) during the first year of life but increased rapidly to values of approximately 200 ng/mg at 20 years of age, which then remained constant until the eighth decade of life. L-Ferritin also showed an increasing trend during life although the concentrations were approximately 50% less than that of H-ferritin at each age point. Neuromelanin was not detectable during the first year, increased to approximately 1000 ng/mg in the second decade and then increased continuously to 3500 ng/mg in the 80th year. A Mossbauer study revealed that the high-spin trivalent iron is probably arranged in a ferritin-like iron--oxyhydroxide cluster form in the substantia nigra. Based on this data and on the low H- and L-ferritin content in neurones it is concluded that neuromelanin is the major iron storage in substantia nigra neurones in normal individuals.

Journal ArticleDOI
TL;DR: Subtypes of GBS defined by preceding infections were only approximately associated with different patterns of clinical, neurophysiologic, and immunologic features, implying interaction with additional host factors.
Abstract: Objective: To test the hypothesis that different preceding infections influence the neurophysiologic classification and clinical features of Guillain–Barre syndrome (GBS) Methods: We tested pretreatment sera, 7 ± 3 (mean ± SD) days from onset, from 229 patients with GBS in a multicenter trial of plasma exchange and immunoglobulin, for serological markers of infection, adhesion molecules, and cytokine receptors, and compared these with neurophysiologic and clinical features Results: Recent infection by Campylobacter jejuni was found in 53 patients (23%), cytomegalovirus in 19 (8%), and Epstein–Barr virus in four (2%) Patients with C jejuni infection were more likely than others to have neurophysiologic criteria of axonal neuropathy or inexcitable nerves, antiganglioside GM 1 antibodies, pure motor GBS, lower CSF protein, and worse outcome Patients with cytomegalovirus infection were younger and more likely than others to have raised serum concentrations of molecules important in T lymphocyte activation and migration, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte selectin, and soluble interleukin-2 receptor (sIL-2R) Concentrations of sICAM-1 and soluble tumor necrosis factor receptor were higher in patients with inexcitable nerves than those with demyelinating neurophysiology Logistic regression analysis showed death or inability to walk unaided at 48 weeks were associated with diarrhea, inexcitable nerves, severe arm weakness, age over 50, raised sIL-2R concentration and absence of immunoglobulin (Ig) M antiganglioside GM 1 antibodies Conclusions: Subtypes of GBS defined by preceding infections were only approximately associated with different patterns of clinical, neurophysiologic, and immunologic features A single infectious agent caused more than one type of pathology in GBS, implying interaction with additional host factors Most patients had no identified infection

Journal ArticleDOI
TL;DR: BDNF and NT-3 levels in post-mortem brain tissue from schizophrenic patients were determined by ELISA and lend further evidence to the neurotrophin hypothesis of schizophrenic psychoses which proposes that alterations in expression of neurotrophic factors could be responsible for neural maldevelopment and disturbed neural plasticity.

Journal ArticleDOI
TL;DR: Results show that forthcoming response effects influence response selection as if these effects were already sensorially present, suggesting that in line with the classical ideomotor theory, anticipated response effects play a substantial role in response selection.
Abstract: This study investigated whether compatibility between responses and their consistent sensorial effects influences performance in manual choice reaction tasks. In Experiment 1 responses to the nonspatial stimulus attribute of color were affected by the correspondence between the location of responses and the location of their visual effects. In Experiment 2, a comparable influence was found with nonspatial responses of varying force and nonspatial response effects of varying auditory intensity. Experiment 3 ruled out the hypothesis that acquired stimulus-effect associations may account for this influence of response-effect compatibility. In sum, the results show that forthcoming response effects influence response selection as if these effects were already sensorially present, suggesting that in line with the classical ideomotor theory, anticipated response effects play a substantial role in response selection.

Journal ArticleDOI
TL;DR: It is argued that by far the most relevant abiotic constraint for growth and vegetative function of vascular epiphytes is water shortage, while other factors such as nutrient availability or irradiation are generally of inferior importance.
Abstract: The current knowledge of the physiological ecology of vascular epiphytes is reviewed here with an emphasis on the most recent literature. It is argued that by far the most relevant abiotic constraint for growth and vegetative function of vascular epiphytes is water shortage, while other factors such as nutrient availability or irradiation, are generally of inferior importance. However, it is shown that the present understanding of epiphyte biology is still highly biased, both taxonomically and ecologically, and it is concluded that any generalizations are still preliminary. Future studies should include a much wider range of taxa and growing sites within the canopy to reach a better understanding how abiotic factors are limiting epiphyte growth and survival which, in turn, should affect epiphyte community composition. Finally, a more integrative approach to epiphyte biology is encouraged: physiological investigations should be balanced by studies of other possible constraints, for example, substrate instability, dispersal limitation, competition or herbivory.

Journal ArticleDOI
TL;DR: Computer-controlled femtosecond polarization pulse shaping where intensity, momentary frequency, and light polarization are varied as functions of time is reported.
Abstract: We report computer-controlled femtosecond polarization pulse shaping where intensity, momentary frequency, and light polarization are varied as functions of time. For the first time to our knowledge, a pulse shaper is used to modulate the degree of ellipticity as well as the orientation of the elliptical principal axes within a single laser pulse by use of a 256-pixel two-layer liquid-crystal display inside a zero-dispersion compressor. Interferometric stability of the setup is not required. Complete pulse characterization is achieved by dual-channel spectral interferometry. This technology has a large range of applications, especially in the field of quantum control.

Journal ArticleDOI
TL;DR: UV-B-dependent inhibition of maximum photochemical yield of photosystem II (PSII), measured as variable fluorescence of dark-adapted leaves, recovered in parallel to the buildup of epidermal screening for UV-B radiation, suggesting that PSII is protected against UV- B damage by epider mal screening.
Abstract: Grape ( Vitis vinifera cv Silvaner ) vine plants were cultivated under shaded conditions in the absence of ultraviolet (UV) radiation in a greenhouse, and subsequently placed outdoors under three different light regimes for 7 d. Different light regimes were produced by filters transmitting natural radiation, or screening out the UV-B (280–315 nm), or screening out the UV-A (315–400 nm) and the UV-B spectral range. During exposure, synthesis of UV-screening phenolics in leaves was quantified using HPLC: All treatments increased concentrations of hydroxycinnamic acids but the rise was highest, reaching 230% of the initial value, when UV radiation was absent. In contrast, UV-B radiation specifically increased flavonoid concentrations resulting in more than a 10-fold increase. Transmittance in the UV of all extracted phenolics was lower than epidermal UV transmittance determined fluorimetrically, and the two parameters were curvilinearly related. It is suggested that curvilinearity results from different absorption properties of the homogeneously dissolved phenolics in extracts and of the non-homogeneous distribution of phenolics in the epidermis. UV-B-dependent inhibition of maximum photochemical yield of photosystem II (PSII), measured as variable fluorescence of dark-adapted leaves, recovered in parallel to the buildup of epidermal screening for UV-B radiation, suggesting that PSII is protected against UV-B damage by epidermal screening. However, UV-B inhibition of CO 2 assimilation rates was not diminished by efficient UV-B screening. We propose that protection of UV-B inactivation of PSII is observed because preceding damage is efficiently repaired while those factors determining UV-B inhibition of CO 2 assimilation recover more slowly.

Journal ArticleDOI
TL;DR: A reverse-genetic system is described for the generation of recombinant coronaviruses based upon the in vitro transcription of infectious RNA from a cDNA copy of the human coronavirus 229E genome that has been cloned and propagated in vaccinia virus.
Abstract: The coronavirus genome is a positive-strand RNA of extraordinary size and complexity. It is composed of approximately 30000 nucleotides and it is the largest known autonomously replicating RNA. It is also remarkable in that more than two-thirds of the genome is devoted to encoding proteins involved in the replication and transcription of viral RNA. Here, a reverse-genetic system is described for the generation of recombinant coronaviruses. This system is based upon the in vitro transcription of infectious RNA from a cDNA copy of the human coronavirus 229E genome that has been cloned and propagated in vaccinia virus. This system is expected to provide new insights into the molecular biology and pathogenesis of coronaviruses and to serve as a paradigm for the genetic analysis of large RNA virus genomes. It also provides a starting point for the development of a new class of eukaryotic, multi-gene RNA vectors that are able to express several proteins simultaneously.

Journal ArticleDOI
15 Sep 2001-BMJ
TL;DR: Botulinum toxin type A was significantly better than placebo on all measures of sweating Patient satisfaction was high and few adverse events were reported Effects of treatment remained apparent at 16 weeks.
Abstract: Objectives: To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design: Multicentre, randomised, parallel group, placebo controlled trial. Setting: 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants: Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions: Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor9s iodine starch test. Main outcome measures: Percentage of responders (patients with ≥50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients9 global assessment of treatment satisfaction score, and adverse events. Results: At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P 0.05). Conclusion: Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topic Primary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and face Current treatments are often ineffective, short acting, or poorly tolerated What this study adds Botulinum toxin type A was significantly better than placebo on all measures of sweating Patient satisfaction was high and few adverse events were reported Effects of treatment remained apparent at 16 weeks