bluuebunny/crossref_metadata_2025 huggingface dataset:
‘La mineraria lavori o lasci lavorare’: myth and memory of a labour struggle in Tuscany
Authors: Fantoni Gianluca
Published: April 2011

This article is an analysis of a long union dispute between the workers and the management of the Società Mineraria del Valdarno (S.M.V.), a company which had mining rights in the lignite basin of Castelnuovo dei Sabbioni, in the municipality of Cavriglia. Cavriglia is in a ‘red zone’ in the province of Arezzo, in central Tuscany and the dispute raged on from the end of 1947 to the first half of the 1950s. The article focuses primarily on two aspects: (1) how the union dispute of the miners of Valdarno fits into the broader political strategy of the Italian Communist Party (PCI); (2) how this struggle was perceived and elaborated by workers and incorporated into the collective memory of local communities.
Sophistopolis as Cosmopolis: Reading Postclassical Greek Rhetoric
Authors: Jarratt Susan C.
Published: April 2011

This article examines the interplay between the Stoic concept of cosmopolis and Greek rhetorical discourses of the polis in the Roman imperial period. D. A. Russell's “Sophistopolis” (from Greek Declamation, 1983) and Doyne Dawson's work on utopian political theory (1992) serve as points of departure for developing a method of reading the political in Second Sophistic rhetoric. The text under examination is a major first-century oration: Dio Chrysostom's Euboean Discourse. Composed around 96 CE, after Dio's return from exile by Domitian, the Euboicus combines a castaway's rural fable with didactic commentary, forcing the utopian pastoral hard up against a lecture on economic and social distress in the imperial city. Dio creates disjunctive moods, city-visions, and speaking personae, performing a rhetorical tour de force while simultaneously constructing a political subject at the limit of creaturely need. A “cosmopolitical” analysis of Second Sophistic rhetoric finds the consummate artistry of the paideia addressed to imperial power and provincial realities, revealing civic breakdown and human suffering in the city-spaces of empire.
Nietzsche's Sophist: Rhêtôr, Musician, Stoic
Authors: Crick Nathan
Published: April 2011

Traditional readings of Nietzsche's essay “On Truth and Lying in a Non-Moral Sense” tend to emphasize the clash between philosophy and rhetoric in the form of two distinct personae—the intuitive, Sophistical artist who embraces the rhetorical power of language to create and destroy on the one hand, and the rational, Stoic philosopher who uses concepts to order the world into a block universe on the other. However, I argue that his essay presents us with not two characters but three—the Stoic philosopher, political rhêtôr, and the Dionysian artist. Furthermore, none of these three characters can be said to be representative of Nietzsche's attitude toward the Sophists. This article thus proposes a model of the Sophistical artist which combines aspects from each of these personae in a way that brings together the power of tragic suffering, persuasive word, and passionate music, respectively. This reading of Nietzsche's work discloses an ideal image of a “new” Sophist as an unfettered spirit for whom Dionysian music and philosophical word cooperate to produce a complex rhetorical discourse capable of overcoming the nihilism of the modern age in order to produce a higher culture. This attitude would therefore make the new Sophist capable of grand aspirations and opportune actions while always remaining cognizant of the sublime and terrible nature that underlies his fragile dreams of beauty.
Creation of a high-temperature plasma through merging and compression of supersonic field reversed configuration plasmoids
Authors: Slough John , Votroubek George , Pihl Chris
Published: April 2011

A new device, the Inductive Plasma Accelerator, was employed to simultaneously form and accelerate two oppositely directed field reversed configurations (FRCs) where the relative velocity (600 km s−1) of the plasmoids was much larger than their internal thermal motion. Upon collision all of the FRC directional energy was observed to be rapidly thermalized concurrent with complete magnetic reconnection of the two FRCs. Upon merging, the resulting FRC was compressed to kilovolt ion temperatures exhibiting a configuration lifetime better than predicted by past scaling of in situ formed FRCs. With the improved FRC confinement scaling, a pulsed plasma device based on this approach capable of achieving fusion gain is examined. For an FRC with a poloidal flux 20 mWb or greater, the fusion energy yield per pulse exceeds the plasma energy for compression fields of 10 T or more. The scaling is insensitive to the compression chamber radial scale, providing for the possibility of a very compact fusion neutron source.
Gex1 is a yeast glutathione exchanger that interferes with pH and redox homeostasis
Authors: Dhaoui Manel , Auchère Françoise , Blaiseau Pierre-Louis , Lesuisse Emmanuel , Landoulsi Ahmed , Camadro Jean-Michel , Haguenauer-Tsapis Rosine , Belgareh-Touzé Naïma
Published: April 2011

In the yeast Saccharomyces cerevisiae, glutathione plays a major role in heavy metal detoxification and protection of cells against oxidative stress. We show that Gex1 is a new glutathione exchanger. Gex1 and its paralogue Gex2 belong to the major facilitator superfamily of transporters and display similarities to the Aft1-regulon family of siderophore transporters. Gex1 was found mostly at the vacuolar membrane and, to a lesser extent, at the plasma membrane. Gex1 expression was induced under conditions of iron depletion and was principally dependent on the iron-responsive transcription factor Aft2. However, a gex1Δ gex2Δ strain displayed no defect in known siderophore uptake. The deletion mutant accumulated intracellular glutathione, and cells overproducing Gex1 had low intracellular glutathione contents, with glutathione excreted into the extracellular medium. Furthermore, the strain overproducing Gex1 induced acidification of the cytosol, confirming the involvement of Gex1 in proton transport as a probable glutathione/proton antiporter. Finally, the imbalance of pH and glutathione homeostasis in the gex1Δ gex2Δ and Gex1-overproducing strains led to modulations of the cAMP/protein kinase A and protein kinase C1 mitogen-activated protein kinase signaling pathways.
Anesthetic Ketamine Impairs Rats' Recall of Previous Information
Authors: Boultadakis Antonios , Pitsikas Nikolaos
Published: April 2011

Background

There is poor experimental evidence concerning the effects of anesthetic doses of the noncompetitive N-methyl-D-aspartate receptor antagonist ketamine on rodents' memory abilities. The current study was designed (1) to investigate the consequences of posttraining administration of anesthetic ketamine (100 mg/kg intraperitoneally) on rats' recognition memory and (2) to evaluate the ability of the nitric oxide synthase inhibitor N-nitro-L-arginine methylester (L-NAME; 1, 3, and 10 mg/kg intraperitoneally) to counteract the expected behavioral deficits produced by anesthetic ketamine. Finally, in an attempt to clarify if the expected memory impairments produced by anesthetic ketamine were related to the anesthesia, we also tested the effects of a subanesthetic dose of it (3 mg/kg intraperitoneally) on rats' recognition memory.

Methods

The novel object recognition test, a procedure assessing recognition memory in rats, was selected.

Results

Posttraining administration of anesthetic (but not of subanesthetic) ketamine disrupted rats' performance in the novel object recognition paradigm. The discrimination index (D) was decreased by ketamine from 0.415 (using saline) to 0.128, thus indicating that the anesthetic dose of ketamine impaired recognition memory. L-NAME (1-3, but not 10, mg/kg) reversed this memory deficit produced by ketamine; the D index of 0.128 using ketamine treatment was increased by 1 and 3 mg/kg L-NAME to 0.427 and 0.478, respectively.

Conclusions

The current results indicate that anesthetic ketamine impaired rats' posttraining memory components (storage and/or retrieval of information) and that a nitric oxide component modulates its behavioral effects.
High-Resolution Secondary Ion Mass Spectrometry Reveals the Contrasting Subcellular Distribution of Arsenic and Silicon in Rice Roots
Authors: Moore Katie L. , Schröder Markus , Wu Zhongchang , Martin Barry G.H. , Hawes Chris R. , McGrath Steve P. , Hawkesford Malcolm J. , Feng Ma Jian , Zhao Fang-Jie , Grovenor Chris R.M.
Published: April 2011

Rice (Oryza sativa) takes up arsenite mainly through the silicic acid transport pathway. Understanding the uptake and sequestration of arsenic (As) into the rice plant is important for developing strategies to reduce As concentration in rice grain. In this study, the cellular and subcellular distributions of As and silicon (Si) in rice roots were investigated using high-pressure freezing, high-resolution secondary ion mass spectrometry, and transmission electron microscopy. Rice plants, both the lsi2 mutant lacking the Si/arsenite efflux transporter Lsi2 and its wild-type cultivar, with or without an iron plaque, were treated with arsenate or arsenite. The formation of iron plaque on the root surface resulted in strong accumulation of As and phosphorous on the epidermis. The lsi2 mutant showed stronger As accumulation in the endodermal vacuoles, where the Lsi2 transporter is located in the plasma membranes, than the wild-type line. As also accumulated in the vacuoles of some xylem parenchyma cells and in some pericycle cells, particularly in the wild-type mature root zone. Vacuolar accumulation of As is associated with sulfur, suggesting that As may be stored as arsenite-phytochelatin complexes. Si was localized in the cell walls of the endodermal cells with little apparent effect of the Lsi2 mutation on its distribution. This study reveals the vacuolar sequestration of As in rice roots and contrasting patterns of As and Si subcellular localization, despite both being transported across the plasma membranes by the same transporters.
Physical and mental health in severe opioid‐dependent patients within a randomized controlled maintenance treatment trial
Authors: Reimer Jens , Verthein Uwe , Karow Anne , Schäfer Ingo , Naber Dieter , Haasen Christian
Published: April 2011

Aims  To evaluate physical and mental health and compare treatment outcomes in opiate‐dependent patients substituted either with heroin or methadone.

Design  Twelve‐month open‐label randomized controlled trial.

Setting  Out‐patient substitution clinics in seven German cities.

Participants  A total of 1015 opiate‐dependent individuals.

Measurements  Opiate Treatment Index–Health Scale Score (OTI), Body Mass Index (BMI), serology for infectious diseases such as hepatitis B, C and human immunodeficiency virus as well as tuberculosis, Karnofsky Performance Scale (KPS), electrocardiogram (ECG), echocardiogram, Symptom Checklist 90‐R (SCL‐90‐R), Global Assessment of Functioning (GAF), Modular System for Quality of Life and study medication‐related serious adverse events (SAE).

Findings  Improvements were found in both heroin and methadone substituted patients regarding OTI, BMI, KPS, SCL‐90‐R, and GAF, but they were more pronounced for the heroin group (analysis of variance, all P = 0.000). The frequency of pathological echocardiograms decreased in the heroin group and increased in the methadone group (χ2 test, <0.05). Markers for infectious diseases and frequencies of pathological ECGs did not differ between baseline and 12 months, or between treatment groups. Study medication‐related serious adverse events, all of which were treated successfully, occurred 2.5 times more often in the heroin group. The majority of heroin‐related SAEs (41 of 58) occurred within a few minutes of the injections.

Conclusions  The integration of severe injection drug users either in methadone or heroin‐assisted maintenance treatment has positive effects on most physical and mental change‐sensitive variables, with heroin showing superior results. Due to medication‐related adverse events, patients should be observed for 15 minutes after a heroin injection.
Tracing genetic differentiation of Chinese Mongolian sheep using microsatellites
Authors: Zhong T. , Han J. L. , Guo J. , Zhao Q. J. , Fu B. L. , Pu Y. B. , He X. H. , Jeon J. T. , Guan W. J. , Ma Y.‐H.
Published: April 2011

The genetic consequences of population differentiation and isolation have been the subject of conservation biology. In this study, we analysed the genetic diversity and structure of Mongolian sheep in China. These animals belong to a traditional local breed with high production, extensive adaption, early maturity and roughage resistance. For this purpose, 26 microsatellites were genotyped for five Mongolian sheep populations. The Bayesian clustering indicated five clusters as the most probable genetic structure of the populations investigated. In addition, a clear genetic structure was revealed in three populations distributed at large geographical scales, while the other cluster encompassed UQ and HLBR sheep that displayed no clear differentiation, probably due to their close and small geographical distributions. Overall, our results are helpful in understanding the interplay of population dynamics in these close genetic lineages of Mongolian sheep.
Cattle and chemokines: evidence for species‐specific evolution of the bovine chemokine system
Authors: Widdison S. , Coffey T. J.
Published: April 2011

The chemokine system comprises a family of small chemoattractant molecules that have roles in both the healthy and diseased organism. Chemokines act by binding specific receptors on the target cell surface and inducing chemotaxis. The human chemokine system is well characterized, with approximately fifty chemokines identified that fall into four families. The chemokines and their receptors are promiscuous in that one chemokine can often bind several receptors, and vice versa. Study of the bovine chemokine system has been restricted to date to a handful of chemokines, and the identification of bovine chemokines is largely based on the closest human homologue. This method of identification is prone to error and may result in the misassumption of function of a particular chemokine. Here, we review current knowledge of bovine chemokines and reassess the bovine chemokine system based on phylogenetic and syntenic approaches. The bovine chemokine system, for the most part, shows high similarity to the chemokine system of other mammals such as humans; however, differences have been identified. Cattle possess fewer chemokines than humans, yet also possess chemokines that have no obvious homologue in the human system. These ‘missing’ and ‘novel’ chemokines may represent functional differences between the bovine and human chemokine systems that may affect the way in which these species are able to respond to specific pathogen repertoires.
Dispersal in the course of an invasion
Authors: NOLTE ARNE W.
Published: April 2011

Invasive species receive attention as manifestations of global ecological change and because of the effects that they may have on other organisms. They are commonly discussed in the context of the ecological perturbations or the human activities that permitted the invasion. There is also evidence, that there is an intrinsic component to biological invasions in that evolutionary changes of the invaders themselves can facilitate or limit invasions (Lee 2002; Urban et al. 2007; Van Bocxlaer et al. 2010). Hence, teasing apart whether environmental change or changes of the organism foster invasions is an interesting field of research. Ample evidence for plants and animals documents that ecological change and human activities trigger range expansions and invasions, but questions regarding evolutionary change of invaders remain less explored although there are several reasons to believe it matters. Firstly, rapid evolutionary change is possible in timeframes relevant for contemporary biological invasions (Hendry et al. 2007). Furthermore, population genetic modelling suggests that there are circumstances where the range expansion and colonization of empty spaces in the course of an invasion can induce evolutionary change in a way that is specific to invaders: the process of repeated founding out of marginal populations in the course of a range expansion can shift allele frequencies and has been referred to as allele surfing, which not only affects neutral genetic variance, but also fitness relevant traits (Klopfstein et al. 2006; Travis et al. 2007; Burton & Travis 2008). Importantly, this process poses a null model for evolutionary inference in invasive populations. It predicts conspicuous allele frequency changes in an expanding metapopulation unless migration homogenizes the gene pool. Despite this relevance, ideas about allele surfing rely heavily on modelling although some experimental evidence comes from studies that document the segregation of genetic variants in growing plaques of bacteria (Hallatschek et al. 2007). To date, little empirical data is available that would reveal the migration processes that affect the establishment of gene pools at invasion fronts in natural systems. This aspect sets the study of Bronnenhuber et al. (2011) apart. They quantify migration behind the expansion front of an invading fish and thus provide important baseline data for the interpretation of the emerging patterns of genetic differentiation.
Circuitry linking the Csr and stringent response global regulatory systems
Authors: Edwards Adrianne N. , Patterson‐Fortin Laura M. , Vakulskas Christopher A. , Mercante Jeffrey W. , Potrykus Katarzyna , Vinella Daniel , Camacho Martha I. , Fields Joshua A. , Thompson Stuart A. , Georgellis Dimitris , Cashel Michael , Babitzke Paul , Romeo Tony
Published: April 2011

CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10‐fold), while they modestly activated csrA expression. We propose that CsrA‐mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT‐PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine‐tunes the stringent response and discuss biological implications of the composite circuitry.
Two gene clusters co‐ordinate for a functional N‐acetylglucosamine catabolic pathway in Vibrio cholerae
Authors: Ghosh Swagata , Rao K. Hanumantha , Sengupta Manjistha , Bhattacharya Sujit K. , Datta Asis
Published: April 2011

Pathogenic microorganisms like Vibrio cholerae are capable of adapting to diverse living conditions, especially when they transit from their environmental reservoirs to human host. V. cholerae attaches to N‐acetylglucosamine (GlcNAc) residues in glycoproteins and lipids present in the intestinal epithelium and chitinous surface of zoo‐phytoplanktons in the aquatic environment for its survival and colonization. GlcNAc utilization thus appears to be important for the pathogen to reach sufficient titres in the intestine for producing clinical symptoms of cholera. We report here the involvement of a second cluster of genes working in combination with the classical genes of GlcNAc catabolism, suggesting the occurrence of a novel variant of the process of biochemical conversion of GlcNAc to Fructose‐6‐phosphate as has been described in other organisms. Colonization was severely attenuated in mutants that were incapable of utilizing GlcNAc. It was also shown that N‐acetylglucosamine specific repressor (NagC) performs a dual role – while the classical GlcNAc catabolic genes are under its negative control, the genes belonging to the second cluster are positively regulated by it. Further application of tandem affinity purification to NagC revealed its interaction with a novel partner. Our results provide a genetic program that probably enables V. cholerae to successfully utilize amino – sugars and also highlights a new mode of transcriptional regulation, not described in this organism.
Tapping into the biofilm: insights into assembly and disassembly of a novel amyloid fibre in Bacillus subtilis
Authors: Driks Adam
Published: April 2011

The Bacillus subtilis biofilm matrix harbours a functionally important amyloid fibre network composed of the protein TasA. Previous studies showed that the protein TapA (formerly YqxM) plays roles in TasA fibre formation and disassembly. In this issue, Romero et al., 2011 show that TapA is a component of the fibre and links it to the peptidoglycan. Therefore, TapA directs TasA fibre formation, links it to the cell wall and, most likely, participates in fibre dispersal. These results provide important insights into the control of biofilm formation in B. subtilis and, potentially, the regulation of amyloid fibre formation in diverse species.
Source verification of mis‐identified Arabidopsis thaliana accessions
Authors: Anastasio Alison E. , Platt Alexander , Horton Matthew , Grotewold Erich , Scholl Randy , Borevitz Justin O. , Nordborg Magnus , Bergelson Joy
Published: April 2011

A major strength of Arabidopsis thaliana as a model lies in the availability of a large number of naturally occurring inbred lines. Recent studies of A. thaliana population structure, using thousands of accessions from stock center and natural collections, have revealed a robust pattern of isolation by distance at several spatial scales, such that genetically identical individuals are generally found close to each other. However, some individual accessions deviate from this pattern. While some of these may be the products of rare long‐distance dispersal events, many deviations may be the result of mis‐identification, in the sense that the data regarding location of origin data are incorrect. Here, we aim to identify such discrepancies. Of the 5965 accessions examined, we conclude that 286 deserve special attention as being potentially mis‐identified. We describe these suspicious accessions and their possible origins, and advise caution with regard to their use in experiments in which accurate information on geographic origin is important. Finally, we discuss possibilities for maintaining the integrity of stock lines.
Antagonistic role of 9‐lipoxygenase‐derived oxylipins and ethylene in the control of oxidative stress, lipid peroxidation and plant defence
Authors: López Miguel A. , Vicente Jorge , Kulasekaran Satish , Vellosillo Tamara , Martínez Marta , Irigoyen Maria L. , Cascón Tomas , Bannenberg Gerard , Hamberg Mats , Castresana Carmen
Published: April 2011

9‐lipoxygenases (9‐LOXs) initiate fatty acid oxygenation in plant tissues, with formation of 9‐hydroxy‐10,12,15‐octadecatrienoic acid (9‐HOT) from linolenic acid. A lox1 lox5 mutant, which is deficient in 9‐LOX activity, and two mutants noxy6 and noxy22 (non‐responding to oxylipins), which are insensitive to 9‐HOT, have been used to investigate 9‐HOT signalling. Map‐based cloning indicated that the noxy6 and noxy22 mutations are located at the CTR1 (CONSTITUTIVE ETHYLENE RESPONSE1) and ETO1 (ETHYLENE‐OVERPRODUCER1) loci, respectively. In agreement, the noxy6 and noxy22 mutants, renamed as ctr1‐15 and eto1‐14, respectively, showed enhanced ethylene (ET) production. The correlation between increased ET production and reduced 9‐HOT sensitivity indicated by these results was supported by experiments in which exogenously added ethylene precursor ACC (1‐aminocyclopropane‐1‐carboxylic acid) impaired the responses to 9‐HOT. Moreover, a reciprocal interaction between ET and 9‐HOT signalling was indicated by results showing that the effect of ACC was reduced in the presence of 9‐HOT. We found that the 9‐LOX and ET pathways regulate the response to the lipid peroxidation‐inducer singlet oxygen. Thus, the massive transcriptional changes seen in wild‐type plants in response to singlet oxygen were greatly affected in the lox1 lox5 and eto1‐14 mutants. Furthermore, these mutants displayed enhanced susceptibility to both singlet oxygen and Pseudomonas syringae pv. tomato, in the latter case leading to increased accumulation of the lipid peroxidation product malondialdehyde. These findings demonstrate an antagonistic relationship between products of the 9‐LOX and ET pathways, and suggest a role for the 9‐LOX pathway in modulating oxidative stress, lipid peroxidation and plant defence.
Achieving STOP TB Partnership goals: perspectives on development of new diagnostics, drugs and vaccines for tuberculosis
Authors: Mwaba Peter , McNerney Ruth , Grobusch Martin Peter , O’Grady Justin , Bates Matthew , Kapata Nathan , Maeurer Markus , Zumla Alimuddin
Published: April 2011

Global eradication of tuberculosis (TB) depends on identification and treatment of all active TB cases and of the two billion people who are estimated to be latently infected with Mycobacterium tuberculosis. The past decade has seen a renaissance of scientific activities and funder investment into development of new TB drugs, diagnostics, biomarkers and vaccines. This viewpoint critically summarises the promising portfolio of more accurate TB diagnostics, new TB drugs and vaccines that have been endorsed by the STOP TB Partnership. Increasing numbers of Phase 2 and 3 drug, vaccine and diagnostic clinical trials in high‐TB endemic areas reflect substantial progress towards attaining Global STOP‐TB Partnership targets. Achievement of STOP‐TB Partnership goals will crucially depend on political will and serious investment by funders and developing country governments into improving delivery of better health services and living conditions for their people. Long‐term sustainability of any newer tools implemented at point of care is essential.
Conserved sequences of thrombospondin‐related adhesive protein gene of Plasmodium vivax in clinical isolates from Korea
Authors: Nam Myung H. , Jang Jin W. , Kim Hanna , Han Eun T. , Lee Won J. , An Seong S. A. , Park Ae S. D. , Lim Chae S.
Published: April 2011

Thrombospondin‐related adhesive protein (TRAP) from Plasmodium vivax (P. vivax) became one of the important vaccine candidates for malaria, because P. vivax TRAP (PvTRAP) is responsible for the sporozoite–host interactions. PvTRAP polymorphisms in the isolates from Republic of Korea (ROK) were analysed, setting the valuable baseline data for the future vaccine developments and clinical trials with PvTRAP, as a strong vaccine candidate. A total of 54 isolates were collected in 2010. PvTRAP genes from above isolates were amplified and sequenced, and the results were analysed and compared against Sal‐1 strain. Sequencing analysis of 1424‐bp‐size PvTRAP PCR products revealed one major allelic type with six non‐synonymous substitutions, where S81T, E95D, I121V and T127R substitutions were found in region II, and K371N and A425E substitutions from region IV. The ROK isolates revealed the limited sequence polymorphisms in PvTRAP in comparison with the reported isolates from other nations.
Use of haplotypes to estimate Mendelian sampling effects and selection limits
Authors: Cole J.B. , VanRaden P.M.
Published: April 2011

Limits to selection and Mendelian sampling (MS) terms can be calculated using haplotypes by summing the individual additive effects on each chromosome. Haplotypes were imputed for 43 382 single‐nucleotide polymorphisms (SNP) in 1455 Brown Swiss, 40 351 Holstein and 4064 Jersey bulls and cows using the Fortran program findhap.f90, which combines population and pedigree haplotyping methods. Lower and upper bounds of MS variance were calculated for daughter pregnancy rate (a measure of fertility), milk yield, lifetime net merit (a measure of profitability) and protein yield assuming either no or complete linkage among SNP on the same chromosome. Calculated selection limits were greater than the largest direct genomic values observed in all breeds studied. The best chromosomal genotypes generally consisted of two copies of the same haplotype even after adjustment for inbreeding. Selection of animals rather than chromosomes may result in slower progress, but limits may be the same because most chromosomes will become homozygous with either strategy. Selection on functions of MS could be used to change variances in later generations.
Wachstumsverhalten humanpathogener Pilze in vitro auf verschiedenen Strumpfgeweben
Authors: Günther A. , Effendy I.
Published: April 2011

Zusammenfassung. Durch ungeeignete Fußbekleidung können bestehende Tinea pedis und Onychomykosen verschlimmert werden. In dieser Studie wurde der Frage nachgegangen, ob die heute üblichen Faserzusammensetzungen von Strümpfen Einfluss auf das Wachstum der humanpathogenen Hautpilze Trichophyton rubrum, Trichophyton mentagrophytes und Candida albicans haben. Zwölf Strumpfproben der Hauptfasergruppen Baumwolle, Schurwolle, synthetische Fasern und Seide sowohl in reiner Form als auch als Mischgewebe wurden mit Suspensionen der Testkeime kontaminiert und die Größen der wachsenden Kolonien gemessen und verglichen. Die Ergebnisse zeigten, dass unterschiedliche Strumpffasern das Wachstum von Pilzen sowohl fördern als auch hemmen können. Alle drei getesteten Hautpilze zeigten eine signifikant hohe Wachstumstendenz auf Polyamid‐Strumpfproben mit hohem Elasthan‐Anteil sowie auf Seidengewirk.

Summary. Athlete's foot and onychomycosis can be aggravated due to inappropriate footwear. In this study we examined whether stockings of synthetic and mixed fabrics may influence the growth behaviour of the commonly isolated fungi Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. A standardized suspension of each fungus was given to each sample of twelve stockings of different materials. The size of the growing colonies and the velocity of their growth were measured and compared to each other. Based on our data stockings depending on their fabric mixture seem to support or inhibit respectively the growth of fungi. Stockings composed of polyamide and a high percentage of polyurethane (Elasthan) and silk stockings as well may likely promote the fungal growth.
Influence of voriconazole and fluconazole on Candida albicans in long‐time continuous flow culture
Authors: Zimmermann Kathrin , Bernhardt J. , Knoke M. , Bernhardt Hannelore
Published: April 2011

Summary. We investigated the influence of voriconazole and fluconazole in a long term trial of continuous flow culture (cfc) up to 9 days. The effects of these azoles were different in dependence on the growth circumstances. Under anaerobic conditions a fungicidal effect of voriconazole was detectable, defined by an inhibition of 99.9%. This also applied to fluconazole for the majority of tested strains of C. albicans. Under aerobic conditions with an otherwise similar situation we found only a fungistatic reaction (inhibition of 90%). Fluorescence microscopy comparing fungal morphology in biofilms on glass surfaces in the cfc revealed a differentiation into blastospores, germ tubes, pseudomycelia and mycelia in the control trial after a cultivation of 8 days. Under anaerobic conditions with azoles only some single cells could be found, sometimes in cell detritus. The adhesion was clearly reduced. Under aerobic conditions more blastospores but no differentiated mycelia were to be seen.

Zusammenfassung. Wir untersuchten den Einfluss von Voriconazol und Fluconazol in kontinuierlicher Langzeitkultur bei einer Zeitdauer bis zu 9 Tagen. Die Wirkung der Azole war unterschiedlich in Abhängigkeit von den Wachstumsbedingungen. Unter anaeroben Verhältnissen zeigte Voriconazol und bei den meisten Teststämmen von Candida albicans auch das Fluconazol eine fungizide Wirkung. Damit wurde eine 99,9%ige Hemmung der C. albicans‐Stämme erreicht. Unter aeroben Bedingungen konnte nur eine 90%ige Hemmung festgestellt werden. Fluoreszenzmikroskopisch wurden nach durchschnittlich achttägiger Kulturdauer große Unterschiede in Morphologie und Biofilmbildung der Pilze auf Glasoberflächen beobachtet. In der Kontrolle ohne Azol‐Zusatz fand sich eine üppige Aufwuchsflora. Die Candida waren differenziert in Blastosporen, Keimschläuche, echte und Pseudomyzelien. Unter Azol‐Einfluss ließ die Besiedlungsdichte deutlich nach. Anaerob waren nur wenige Sprosszellen, selten einmal ein Keimschlauch, häufig nur Zelldetritus nachweisbar. Die Adhäsion war deutlich herabgesetzt. Aerob waren mehr Blastosporen und keine differenzierten Myzelien vorhanden.
Beobachtungen zur Blutgerinnung bei einheimischen tiefen Mykosen
Authors: Ntefidou Maria , Elsner Christine , Spreer Annette , Weinstock N. , Kratzin H. D. , Rüchel R.
Published: April 2011

Zusammenfassung. Die Aktivierung der Blutgerinnung tritt in unterschiedlichem Maß bei invasiven einheimischen Mykosen auf. Während es bei Candidosen und Aspergillosen nach Einbruch der Pilze in die Blutbahn gelegentlich zur Bildung von Thromben kommt, die zu septischen Embolien Anlass geben können, werden bei Mucormykosen (Syn. Zygomykosen) regelmäßig ausgedehnte thrombotische Verschlüsse der befallenen Gefäße und folglich Nekrosen des abhängigen Gewebes beobachtet. Für die Auslösung der Gerinnung durch Candida und Aspergillen können sekretorische Aspartat‐Proteinasen der Pilze verantwortlich sein, die den Gerinnungsfaktor X aktivieren, wie bereits früher gezeigt wurde [1, 2]. Für die gravierenden Gerinnungsereignisse bei Mucormykosen ist hingegen offenbar eine extrazelluläre subtilisin‐ähnliche Serinproteinase (Arp) verantwortlich, die bereits in geringen Konzentrationen bei Raumtemperatur eine Parakoagulation von Fibrinogen auslöst, und die zugleich den wichtigsten Inhibitor der Gerinnung, das Antithrombin III, zerstört. Neue Befunde zur Wirkung von Arp werden diskutiert.

Summary. Activation of blood coagulation to a varying extent affect the course of domestic invasive mycoses. Upon invasion of blood vessels by Candida or aspergilli, occasionally thrombi are formed, which may cause septic embolism. In the course of mucormycosis (syn. zygomycosis) thrombotic occlusion of afflicted blood vessels and subsequent necrosis of dependent tissue regularly occurs. Coagulation during candidosis or aspergillosis may be triggered by secreted aspartic proteinases which are able to activate factor X as has been shown previously [1, 2]. During mucormycosis, severe blood coagulation apparently is due to paracoagulation of fibrinogen which is triggered by low concentrations of extracellular fungal subtilisin‐like proteinase (Arp). The enzyme is also able to inactivate the major inhibitor of blood coagulation (antithrombin III). Recent findings on the action of Arp are discussed.
Die Dermatomykologie im geschichtlichen Überblick
Authors: Mittag Hannelore
Published: April 2011

Zusammenfassung. Diese Übersicht bezieht sich im ersten Abschnitt auf klinische Aspekte in der Geschichte der Dermatomykologie, im zweiten Teil kommt die Phase der Entdeckung der Pilze bei bestimmten Hauterkrankungen im 19. Jh. zur Sprache, was den Beginn der Dermatomykologie kennzeichnete. Es wird auf die Bedeutung der Interaktion von Pilzen und Wirtsorganismus in diesem Kontext hingewiesen und auch auf erste Untersuchungen, die zu dieser Thematik an Pflanzen am Ende des 17. Jahrhunderts von Marcello Malpighi durchgeführt wurden, aufmerksam gemacht.

Summary. This historical review is focussed on clinical aspects of dermatomycology on one hand and on the discovery of fungi as pathogenic agents in dermatologic diseases on the other hand. This latter period in the 19th century established the beginning of dermatomycology. The basic role of fungus‐host‐interrelationship is mentioned with reference to earliest microscopical investigations of this issue on plants by Marcello Malphighi in the late 17th century.
Wirkungsweise von Ciclopiroxolamin auf Candida albicans
Authors: Niewerth M. , Schaller M. , Korting H. C. , Hube B.
Published: April 2011

Zusammenfassung. Candida albicans ist ein häufiger Erreger sowohl superfizieller als auch invasiver Mykosen. Zu den therapeutisch verwendeten Antimykotika bei oberflächlichen Candidosen gehört das Hydroxypyridon Ciclopiroxolamin. Während die Wirkungsweise anderer Antimykotika wie zum Beispiel der Azole gut bekannt ist, kennt man die Wirkung des Ciclopiroxolamins nur ansatzweise. Es gibt Hinweise, daß Ciclopiroxolamin als potentieller Chelatbildner auf eine ganze Reihe von zellulären Prozessen einen Einfluß ausübt. Die antimykotische Wirksamkeit von Ciclopiroxolamin könnte daher zum Beispiel sowohl auf eine allgemein eingeschränkte Lebensfähigkeit des Pilzes gegenüber dem menschlichen Immunsystem als auch auf eine reduzierte Fähigkeit, bestimmte Virulenzfaktoren zu produzieren, zurückzuführen sein. Eine zentrale Rolle hierbei scheint jedoch der Eisenstoffwechsel zu spielen.

Summary. Candida albicans is a common pathogen causing both superficial and invasive mycoses. The hydroxypyridone ciclopiroxolamine belongs to antimycotic drugs used for treatment of superficial mycoses. Whereas the mode of action of other antimycotics, for example the azoles, is well known, the specific action of ciclopiroxolamine is poorly understood. There are hints, that ciclopiroxolamine acts as a potential chelating agent and influences some cellular processes by chelating metal ions. Consequently, the antimycotic effectiveness of ciclopiroxolamine could be due to a general reduced viability of the fungus, or due to a higher sensitivity of a fungus against the human immune system as well as due to a reduced capability to produce some specific virulence factors that are indispensable for infection. Nevertheless, iron metabolism seems to play a major role in its effect.
Zur Geschichte der medizinischen Mykologie in der ehemaligen DDR*
Authors: Seebacher C. , Blaschke‐Hellmessen Renate , Kielstein P.
Published: April 2011

Zusammenfassung. Die Entwicklung der medizinischen Mykologie verlief in Deutschland nach dem Zweiten Weltkrieg ‐ bedingt durch die staatliche Teilung‐ in Ost und West unterschiedlich. Der Beitrag beschäftigt sich mit der Situation in der ehemaligen DDR. Aus anfänglich vorwiegend an Hautkliniken bestehenden mykologischen Laboratorien wurden nach und nach leistungsfähige Zentren an fast allen medizinischen Hochschulen eingerichtet, die für die Diagnostik, aber auch für Lehre und Forschung zuständig waren. Hauptleistungsträger waren dabei vor allem Diplombiologinnen und ‐biologen, die in den Hochschulbetrieb schließlich weitgehend gleichberechtigt neben Ärzten integriert waren.

Das Wirken der Gesellschaft für Medizinische Mykologie der DDR, ihre Vorstände und Arbeitsgemeinschaften sowie die Schwerpunkte der human‐ und veterinärmedizinischen Mykologie während dieser Periode werden dargelegt. Im Besonderen wird der problemlose Beitritt dieser Gesellschaft zur Deutschsprachigen Mykologischen Gesellschaft nach der Wiedervereinigung Deutschlands und das aktive Mitwirken von Prof. Dr. Johannes Müller bei diesem Prozess hervorgehoben.

Summary. After the Second World War the development of medical mycology in Germany had taken a very different course in the east and west parts depending on the political division. In this respect our contribution deals with the situation in the former German Democratic Republic. Efficient mycological centres were founded step by step almost in all medical universities on the basis of the mycological laboratories in dermatological hospitals competent for diagnostic work, but also for teaching and scientific research. In this context biologists were the main stay of mycology, they finally were integrated to the same degree in the universities like physicians. The effectiveness of the Gesellschaft für Medizinische Mykologie der DDR (GMM), its board of directors and its working groups as well as the topics of human and animal mycology during this period are described. Especially the merger of the GMM with the Deutschsprachige Mykologische Gesellschaft after the reunification of Germany without problems and the kind co‐operation of Prof. Dr. Johannes Müller during this procedure are emphasized.
Systemische Candida‐Infektionen bei Intensivpatienten
Authors: Glöckner A.
Published: April 2011

Zusammenfassung. Die Inzidenz der invasiven Candidose ist weltweit steigend und die Letalität weiterhin sehr hoch. Die diagnostischen Schritte, die Wertung von entsprechenden Untersuchungsergebnissen sowie die Indikationsstellung zur antimykotischen Therapie stellen auf der Intensivtherapiestation ein Problem dar. Somit kommt der Erkennung von Risikofaktoren eine große Bedeutung zu. Der Einsatz der Antimykotika ist häufig durch ein inadäquates Spektrum, die Applikationsform oder die Nebenwirkungen limitiert. Neue Präparate geben Hoffnung für die nahe Zukunft.

Summary. The incidence of invasive candidosis is increasing worldwide and the mortality is high. In the intensive care unit diagnostic measurements, correct evaluation of the findings and the right indication for antifungal treatment remain problematic. So determination of potential risk factors is very important. The therapeutic use of antifungal drugs is often limited by important disadvantages like inadequate spectrum, application form or side effects. New antifungals give hope for the near future.
Amphotericin B und seine Lipid‐Formulierungen
Authors: Ritter J.
Published: April 2011

Zusammenfassung. Die vor über 40 Jahren eingeführte Behandlung mit Amphotericin B stellt nach wie vor den Goldstandard bei der Behandlung invasiver Pilzinfektionen mit Hefe‐ oder Schimmelpilzen dar. Seit mehr als 10 Jahren sind drei verschiedene Lipid‐Formulierungen von Amphotericin B verfügbar, von denen derzeit in Deutschland nur das liposomale Amphotericin B (Ambisome®) zugelassen ist.

Wegen der geringeren Nephrotoxizität, der besseren subjektiven Verträglichkeit — bei gleicher bzw. höherer Wirksamkeit — sowie der Möglichkeit einer höher dosierten Therapie zu Beginn der Behandlung (loading‐dose) ist die liposomale Form von Amphotericin B dem konventionellen Amphotericin B überlegen.

Summary. More than 40 years after its approval, Amphotericin B is still the gold standard in the treatment of invasive fungal infections due to Candida and Aspergillus spp. Three different lipid formulations of Amphotericin B have been available for over 10 years, with only one of them, i.e. liposomal Amphotericin B (Ambisome®), approved in Germany.

Liposomal Amphotericin B is superior to conventional Amphotericin B due to its reduced nephrotoxicity, the option of a higher initial loading‐dose, and fewer infusion‐related side‐effects, all this with identical or even higher efficacy.
Voriconazol — Perspektiven und klinische Aspekte
Authors: Ruhnke M.
Published: April 2011

Zusammenfassung. Der Wirkstoff von Vfend® ist Voriconazol, ein neues Antimykotikum aus der Gruppe der Triazole mit sehr breitem Wirkspektrum. Die Wirksamkeit wurde gegen Sproßpilz‐Arten wie Candida‐Species und Cryptococcus neoformans sowie gegen diverse Fadenpilze, insbesondere die Aspergillus‐Species, aber auch dimorphe Pilze in vitro und in vivo (in Tierexperimenten) nachgewiesen. In klinischen Phase‐II‐ und Phase‐III‐Studien konnte die Wirksamkeit insbesondere bei der oralen und ösophagealen Candidose sowie der akut invasiven und chronisch‐invasiven Aspergillose nachgewiesen werden. Das bisher bekannte Nebenwirkungsspektrum gleicht dem anderer Triazole, bis auf ein vermehrtes Auftreten von Sehstörungen. Für den Einsatz in der Therapie invasiver Mykosen stellt Voriconazol eine deutliche Bereicherung dar. In der Behandlung der akut invasiven Aspergillosen ist Voriconazol dem Amphotericin B‐Desoxycholat überlegen.

Summary. Voriconazole (Vfend®) is a new broadspectrum antifungal agent belonging to the group of triazole drugs. In vitro and in vivo efficacy was demonstrated against a large variety of yeasts with excellent activity against all Candida species but as well against Cryptococcus neoformans. Furthermore, voriconazole has shown excellent activity against many moulds in particular against Aspergillus species, but endemic fungi such as Histoplasma capsulatum are in the spectrum as well. Clinical efficacy was demonstrated in several large phase II/III studies in diseases such as oral and oesophageal candidosis, acute invasive aspergillosis or chronic invasive aspergillosis. New adverse events such as visual disturbances has been described together with the use of voriconazole, but the majority of adverse events are similar to other triazole drugs and in particular not life‐threatening. With the introduction of voriconazole a great progress in the therapy of invasive fungal infections was achieved. In the therapy of invasive aspergillosis, voriconazole is significantly more effective compared to amphotericin B desoxycholate.
The first echinocandin: caspofungin
Authors: Cornely O.A. , Schmitz Karina , Aisenbrey Sabine
Published: April 2011

Summary. The antifungal agent caspofungin is the first echinocandin that has been approved in the US and in Europe for treatment of invasive aspergillosis in adult patients who are refractory to or intolerant of conventional amphotericin B, its lipid‐based formulations, and/or itraconazole. It is given as a 70 mg loading dose and a 50 mg daily maintainance dose as a one hour infusion. Due to low intestinal absorption an oral formulation has not been developed. Caspofungin is active against Candida spp. and Aspergillus spp. by inhibition the synthesis of β‐(1,3)‐D‐glucan, a cell wall component. The drug is inactive against Cryptococcus spp., Fusarium spp., Trichosporon spp., Rhizopus spp., and Pseudoallescheria spp. In invasive aspergillosis caspofungin resulted in higher response rates compared to a historic control under standard therapy. Efficacy data on persistently febrile neutropenic patients are pending. In several multicenter randomised double blind trials on candida infections caspofungin proved to be at least non‐inferior to standard therapies. Reports of combination therapy or highly effective antifungal treatment (HEAT) in limited patient numbers are promising. New trials of combination therapy are warranted.

Zusammenfassung. Caspofungin ist das erste Antimykotikum aus der Klasse der Echinocandine. Es ist in den USA und in Europa zugelassen zur Therapie invasiver Aspergillosen erwachsener Patienten, die auf eine Standardtherapie nicht ansprechen oder diese nicht vertragen. Caspofungin wird am ersten Tag mit 70 mg dosiert und danach mit einer Erhaltungsdosis von 50 mg als einstündige Infusion verabreicht. Wegen seiner geringen enteralen Resorption ist eine orale Formulierung nicht entwickelt worden. Caspofungin ist wirksam gegen Candida spp. und Aspergillus spp. durch die Inhibition der Synthese des β‐(1,3)‐D‐Glucans, das ein Bestandteil der Zellwand ist. Die Substanz ist unwirksam gegenüber Cryptococcus spp., Fusarium spp., Trichosporon spp., Rhizopus spp., und Pseudoallescheria spp. In der Therapie der invasiven Aspergillose war Caspofungin effektiver als Standardtherapien in einem historischen Vergleichskollektiv. Daten zur Effektivität persistierend febriler neutropenischer Patienten werden erwartet. In einigen randomisierten multizentrischen doppel‐blinden Studien zu Candida‐Infektionen zeigte sich Caspofungin zumindest als nicht‐unterlegen im Vergleich zu Standardtherapien. Berichte über Kombinationstherapien, die sog. hocheffektive antimykotische Therapie (HEAT) begrenzter Patientenzahlen sind vielversprechend. Weiter führende Kombinationsstudien sind erforderlich.