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Objective: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca2+ influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets.
Methods: Islets were isolated from female C57BL/6J mice (J-islets), which lack functional NNT, and genetically close C57BL/6N mice (N-islets). Wild-type mouse NNT was expressed in J-islets by adenoviral infection. Mitochondrial and cytosolic glutathione oxidation was measured with glutaredoxin 1-fused roGFP2 probes targeted or not to the mitochondrial matrix. NADPH and NADH redox state was measured biochemically. Insulin secretion and upstream coupling events were measured under dynamic or static conditions by standard procedures.
Results: NNT is largely responsible for the acute glucose-induced rise in islet NADPH/NADP+ ratio and decrease in mitochondrial glutathione oxidation, with a small impact on cytosolic glutathione. However, contrary to current views on NNT in β-cells, these effects resulted from a glucose-dependent reduction in NADPH consumption by NNT reverse mode of operation, rather than from a stimulation of its forward mode of operation. Accordingly, the lack of NNT in J-islets decreased their sensitivity to exogenous H2O2 at non-stimulating glucose. Surprisingly, the lack of NNT did not alter the glucose-stimulation of Ca2+ influx and upstream mitochondrial events, but it markedly reduced both phases of GSIS by altering Ca2+-induced exocytosis and its metabolic amplification.
Conclusion: These results drastically modify current views on NNT operation and mitochondrial function in pancreatic β-cells.
HADES is a fixed target experiment using SIS18 heavy-ion beams. It investigates the microscopic properties of matter formed in heavy-ion, proton and pion - induced reactions in the 1-3.5 GeV/u energy regime. In 2014 HADES used a secondary pion beam produced by interaction between high-intensity nitrogen primary beam and a beryllium target. In these conditions beam losses, generated by slow extraction and beam transport to the experimental area, led to activation of the beam line elements and triggered radiation alarms. The primary beam intensity had to be reduced and the beam optics modified in order to keep radiation levels within the allowed limits. Similar beam conditions are requested by HADES experiment for upcoming run in 2018 and in the following years. Therefore, a number of measures have been proposed to improve beam transmission and quality. These measures are: additional shielding, additional beam instrumentation, modification of beam optics and increase of vacuum chambers' apertures in critical locations. The optics study and preliminary results of FLUKA simulations for optimization of location of loss detectors are presented.
Excessive neutrophil activation accompanied by delayed apoptotic cell death in inflammatory conditions causes progressive damage of cells and tissues, leading to life-threatening multiple organ dysfunction syndrome. Previous work suggested that circulating serum factors during inflammation are critically involved in the suppression of neutrophil cell death although the identity of these antiapoptotic mediators remained elusive. In this study, we identified the acute phase protein α-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced apoptosis in human neutrophils through a mechanism implicating caspases-independent pathways. We show here that serum levels of AAT, potentially in part released by stimulated neutrophils, are markedly elevated in major trauma patients suffering from systemic inflammatory response syndrome (SIRS). Notably, AAT depletion from serum increased sensitivity of human neutrophils for STS-induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis resistance by preventing PKC/Akt inactivation and subsequent proteasomal degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered antiapoptotic pathways in neutrophils. In summary, these results establish a novel pivotal role of circulating AAT in mediating survival by antagonizing the proapoptotic action of the PKC inhibitor STS and should be considered for AAT augmentation therapies in future.
The efficacy of cisplatin-based chemotherapy in cancer is limited by the occurrence of innate and acquired drug resistance. In order to better understand the mechanisms underlying acquired cisplatin resistance, we have compared the adenocarcinoma-derived non-small cell lung cancer (NSCLC) cell line A549 and its cisplatin-resistant sub-line A549rCDDP2000 with regard to cisplatin resistance mechanisms including cellular platinum accumulation, DNA-adduct formation, cell cycle alterations, apoptosis induction and activation of key players of DNA damage response. In A549rCDDP2000 cells, a cisplatin-induced G2/M cell cycle arrest was lacking and apoptosis was reduced compared to A549 cells, although equitoxic cisplatin concentrations resulted in comparable platinum-DNA adduct levels. These differences were accompanied by changes in the expression of proteins involved in DNA damage response. In A549 cells, cisplatin exposure led to a significantly higher expression of genes coding for proteins mediating G2/M arrest and apoptosis (mouse double minute 2 homolog (MDM2), xeroderma pigmentosum complementation group C (XPC), stress inducible protein (SIP) and p21) compared to resistant cells. This was underlined by significantly higher protein levels of phosphorylated Ataxia telangiectasia mutated (pAtm) and p53 in A549 cells compared to their respective untreated control. The results were compiled in a preliminary model of resistance-associated signaling alterations. In conclusion, these findings suggest that acquired resistance of NSCLC cells against cisplatin is the consequence of altered signaling leading to reduced G2/M cell cycle arrest and apoptosis.
Recruitment of inflammatory cells is a major feature of alcoholic liver injury however; the signals and cellular sources regulating this are not well defined. C-C chemokine receptor type 2 (CCR2) is expressed by active hepatic stellate cells (HSC) and is a key monocyte recruitment signal. Activated HSC are also important sources of hydrogen peroxide resulting from the activation of NADPH oxidase 4 (NOX4). As the role of this NOX in early alcoholic liver injury has not been addressed, we studied NOX4-mediated regulation of CCR2/CCL2 mRNA stability. NOX4 mRNA was significantly induced in patients with alcoholic liver injury, and was co-localized with αSMA-expressing activated HSC. We generated HSC-specific NOX4 KO mice and these were pair-fed on alcohol diet. Lipid peroxidation have not changed significantly however, the expression of CCR2, CCL2, Ly6C, TNFα, and IL-6 was significantly reduced in NOX4HSCKO compared to fl/fl mice. NOX4 promoter was induced in HSC by acetaldehyde treatment, and NOX4 has significantly increased mRNA half-life of CCR2 and CCL2 in conjunction with Ser221 phosphorylation and cytoplasmic shuttling of HuR. In conclusion, NOX4 is induced in early alcoholic liver injury and regulates CCR2/CCL2 mRNA stability thereby promoting recruitment of inflammatory cells and production of proinflammatory cytokines.
Erwin Wittstock (1899-1962), the writer of German expression from Romania, has created a monumental body of works (short stories and novels), which stem from German history and culture from Transylvania. The characters he created are projections of his own life. His novel Januar ’45 oder Die höhere Pflicht, reviewed in the present article from an intercultural point of view, is dedicated to the problem of deportation, a topic which was taboo in the communist regime. His work on the topic is shaped into a novel in Balzacian style, the author writing from the perspective of an eye witness. The problematic invites the description of power, of terror and of repression in totalitarian states. As member of the German community in Romania he depicts the Transylvanian multiethnic and multicultural society in his fiction. The elements of interculturality in his novel can be summarized as: social interethnic relations, imagology, respectively the outlining of the image of otherness, also on a linguistic level.
We derive three exact sum rules for the spectral function of the electromagnetic current with zero spatial momentum at finite temperature. Possible applications of the three sum rules to lattice computations of the spectral function and transport coefficients are also discussed: We propose an ansatz for the spectral function that can be applied to all three sum rules and fit it to available lattice data of the Euclidean vector correlator above the critical temperature. As a result, we obtain estimates for both the electrical conductivity σ and the second order transport coefficient τJ.
Was Du heute kannst besorgen, das verschiebe nicht auf morgen: Dieser sprichwörtliche Rat kommt nicht von ungefähr. Viele von uns schieben oft wochenlang eine Aufgabe vor sich her – häufig mit schlechtem Gewissen. Doch woher kommt das ewige Aufschieben eigentlich? Wer ist davon betroffen? Und was kann man dagegen tun?
Der Mensch besteht aus vielen Körperteilen, und doch ist es fast ausschließlich das Gesicht, an dem wir ein Individuum erkennen. Aber erkennen wir es wirklich? In Zeiten des Selfie-Kults und der biometrischen Verfahren ist diese Frage aktueller denn je. Wir leben in einer »fazialen« Gesellschaft: Das Gesicht ist Medium für alle erdenklichen Arten, sich mitzuteilen.
Verschlafen? Ausgeschlafen!
(2017)
The bilingual phraseography with German contains significant shortcomings regarding both the conceptional orientation of the dictionary and the structure of the dictionary articles. The present paper reflects upon the relevance of certain criteria that are decisive for the quality of a dictionary and aims at showing to what extent the description of the selected phraseologisms is adequate with regard to potential users and the specifics of phraseological phenomena.
Based on the specific use of fixed expressions in everyday communication or in written messages, the paper presents modifications of reiterated discourse (suppresion, addition, substitution, permutation) that are illustrated by adapted common phrases and innovations of text types with formalized language.
Cette étude analyse les stratégies locales de dénomination des espèces végétales par les Mossé des régions du nord, du centre nord, du centre et du Plateau Central du Burkina Faso et leurs perceptions des plantes. A travers des interviews semi directes auprès de 1437 personnes âgées d’au moins 60 ans et des jeunes de moins de 40 ans des différentes localités, l’étude a pu montrer les critères de dénomination, les conceptions que les populations ont des espèces végétales ainsi que l‘impact de ces connaissances dans la conservation de la phytodiversité. 72 espèces au total ont été décrites. Elles sont réparties en 51 genres et 29 familles. Les familles dominantes sont les Commelinaceae et les Fabaceae-Mimosoideae. Dans la taxonomie locale faite sur les plantes en milieu rural Mossé, 16 critères sont utilisés. Les critères les plus cités par la population sont l’usage fait de la plante (94 %), le mysticisme lié à l’espèce (86 %), l’écologie ou le milieu de vie de l’espèce (83 %), la dualité mâle/femelle (83 %), la couleur des organes ou parties de la plante (81 %), l’origine de la plante (80 %), la morphologie foliaire (76 %), la présence d’organes saillants sur la plante (75 %) et le mode de dissémination des fruits ou des graines (74 %). Les noms botaniques attribués aux plantes varient d’une région à une autre. Les populations ont des perceptions vis-à-vis de nombreuses espèces. Ainsi, les espèces comme Stereospermum kunthianum, Calotropis procera, Ozoroa insignis, Faidherbia albida, Maytenus senegalensis et Biophytum umbraculum sont frappées de mysticisme. Elles sont toutes craintes par les populations et sont dans certaines localités à l’abri d’exploitations multiformes humaines. Cela contribue à une meilleure conservation de la biodiversité.
Com o advento da modernidade a filosofia passou a exigir que a religião prestasse contas à razão. A filosofia da religião de Kant é um exemplo desse tipo de iniciativa. Kant propôs julgar a religião no tribunal da razão. Mais de 200 anos depois, Habermas buscou renovar o projeto kantiano. Nosso trabalho visa esclarecer o modo como cada autor realiza o julgamento da religião no tribunal da razão. Além disso, discutiremos a relevância desse tipo de abordagem proposta por ambos os filósofos.
In mammals, acoustic communication plays an important role during social behaviors. Despite their ethological relevance, the mechanisms by which the auditory cortex represents different communication call properties remain elusive. Recent studies have pointed out that communication-sound encoding could be based on discharge patterns of neuronal populations. Following this idea, we investigated whether the activity of local neuronal networks, such as those occurring within individual cortical columns, is sufficient for distinguishing between sounds that differed in their spectro-temporal properties. To accomplish this aim, we analyzed simple pure-tone and complex communication call elicited multi-unit activity (MUA) as well as local field potentials (LFP), and current source density (CSD) waveforms at the single-layer and columnar level from the primary auditory cortex of anesthetized Mongolian gerbils. Multi-dimensional scaling analysis was used to evaluate the degree of “call-specificity” in the evoked activity. The results showed that whole laminar profiles segregated 1.8-2.6 times better across calls than single-layer activity. Also, laminar LFP and CSD profiles segregated better than MUA profiles. Significant differences between CSD profiles evoked by different sounds were more pronounced at mid and late latencies in the granular and infragranular layers and these differences were based on the absence and/or presence of current sinks and on sink timing. The stimulus-specific activity patterns observed within cortical columns suggests that the joint activity of local cortical populations (as local as single columns) could indeed be important for encoding sounds that differ in their acoustic attributes.
Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus. While laboratory strains (HIV-1NL4.3 and HIV-1IIIB) are sensitive to SUN1-mediated inhibition, the transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of sensitivity to SUN1, and in vitro-assembled capsid-nucleocapsid (CANC) nanotubes captured SUN1 and SUN2 from cell lysates. Finally, we generated SUN1−/− and SUN2−/− cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect. Taken together, these observations suggest that SUN1 and SUN2 may function redundantly to modulate postentry, nuclear-associated steps of HIV-1 infection.
IMPORTANCE HIV-1 causes more than 1 million deaths per year. The life cycle of HIV-1 has been studied extensively, yet important steps that occur between viral capsid release into the cytoplasm and the expression of viral genes remain elusive. We propose here that the INM components SUN1 and SUN2, two members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may interact with incoming HIV-1 replication complexes and affect key steps of infection. While overexpression of these proteins reduces HIV-1 infection, disruption of the individual SUN2 and SUN1 genes leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis.
Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially expressed genes that are linked to morphological alterations of gonadal tissue from chicken embryos after exposure to TBT. We applied a single injection of TBT (between 0.5 and 30 pg as Sn/g egg) into incubated fertile eggs to simulate maternal transfer of the endocrine disruptive compound. Methyltestosterone (MT) served as a positive control (30 pg/g egg). After 19 days of incubation, structural features of the gonads as well as genome-wide gene expression profiles were assessed simultaneously. TBT induced significant morphological and histological malformations of gonadal tissue from female embryos that show a virilization of the ovaries. This phenotypical virilization was mirrored by altered expression profiles of sex-dependent genes. Among these are several transcription and growth factors (e.g. FGF12, CTCF, NFIB), whose altered expression might serve as a set of markers for early identification of endocrine active chemicals that affect embryonic development by transcriptome profiling without the need of elaborate histological analyses.
Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients
(2017)
Background: Mutations in the KCNJ2 gene encoding the ion channel Kir2.1 have been linked to the Andersen-Tawil syndrome (ATS). Molecular genetic screening performed in a family exhibiting clinical ATS phenotypes unmasked a novel sequence variant (c.434A > G, p.Y145C) in this gene. The aim of this study was to investigate the effect of this variant on Kir2.1 ion channel functionality.
Methods: Mutant as well as wild type GFP tagged Kir2.1 channels were expressed in HEK293 cells. In order to examine the effect of the new variant, electrophysiological measurements were performed using patch clamp technique. Cellular localization of the mutant in comparison to the wild type ion channel was analyzed by confocal laser scanning microscopy.
Results: The currents of cells expressing only mutant channels or a mixture of wild type and mutant were significantly reduced compared to those expressing wild type (WT) channels (p < 0.01). Whereas WT expressing cells exhibited at −120 mV an averaged current of −4.5 ± 1.9 nA, the mutant generates only a current of −0.17 ± 0.07 nA. A co-expression of mutant and WT channel generates only a partial rescue of the WT current. Confocal laser scanning microscopy indicated that the novel variant is not interfering with synthesis and/or protein trafficking.
Conclusions: The detected sequence variant causes loss-of-function of the Kir2.1 channel and explains the clinical phenotypes observed in Andersen-Tawil syndrome patients.
Molluscs are the second most species-rich phylum in the animal kingdom, yet only 11 genomes of this group have been published so far. Here, we present the draft genome sequence of the pulmonate freshwater snail Radix auricularia. Six whole genome shotgun libraries with different layouts were sequenced. The resulting assembly comprises 4,823 scaffolds with a cumulative length of 910 Mb and an overall read coverage of 72×. The assembly contains 94.6% of a metazoan core gene collection, indicating an almost complete coverage of the coding fraction. The discrepancy of ∼690 Mb compared with the estimated genome size of R. auricularia (1.6 Gb) results from a high repeat content of 70% mainly comprising DNA transposons. The annotation of 17,338 protein coding genes was supported by the use of publicly available transcriptome data. This draft will serve as starting point for further genomic and population genetic research in this scientifically important phylum.
The effect-response framework states that plant functional traits link the abiotic environment to ecosystem functioning. One ecosystem property is the body size of the animals living in the system, which is assumed to depend on temperature or resource availability, among others. For primary consumers, resource availability may directly be related to plant traits, while for secondary consumers the relationship is indirect. We used plant traits to describe resource availability along an elevational gradient on Mount Kilimanjaro, Tanzania. Using structural equation models, we determined the response of plant traits to changes in precipitation, temperature and disturbance with and assessed whether abiotic conditions or community-weighted means of plant traits are stronger predictors of the mean size of bees, moths, frugivorous birds, and insectivorous birds. Traits indicating tissue density and nutrient content strongly responded to variations in precipitation, temperature and disturbance. They had direct effects on pollination and fruit traits. However, the average body sizes of the animal groups considered could only be explained by temperature and habitat structure, not by plant traits. Our results demonstrate a strong link between traits and the abiotic environment, but suggest that temperature is the most relevant predictor of mean animal body size. Community-weighted means of plant traits and body sizes appear unsuitable to capture the complexity of plant-animal interactions.
Wer spricht wie über wen? Diese Frage wird im Folgenden an die dokumentarischen Kinderhörspiele Kinder auf der Flucht, damals und heute (2015) und Jeden Tag ein bisschen ankommen. Flüchtlingskinder in einer Dortmunder Willkommensklasse (2015) als Erzählformen über Migration und Flucht, die repräsentative und identitätsstiftende Angebote machen, gestellt. An diesen Aspekten setzen kritische Fragen nach der Möglichkeit der Artikulation von Kindern als GestalterInnen postmigrantischen Zusammenlebens an. Dabei wird speziell in den Blick genommen, ob und wie Kinder als bevormundete Personen, die darüber hinaus durch den Status geflüchtet markiert sind, einer doppelten Herausforderung des Sprechens und Gehörtwerdens begegnen. Der Fokus der Untersuchung richtet sich darauf, wie in den Radiogeschichten das Verhältnis von Originalton-Material und personifizierter Erzählinstanz gestaltet ist, welche definierenden Konzepte und Begriffe zum Einsatz kommen und wo sich subversive Erzählmomente finden lassen. ...
Feeding type and development drive the ingestion of microplastics by freshwater invertebrates
(2017)
Microscopic plastic items (microplastics) are ubiquitously present in aquatic ecosystems. With decreasing size their availability and potential to accumulate throughout food webs increase. However, little is known on the uptake of microplastics by freshwater invertebrates. To address this, we exposed species with different feeding strategies to 1, 10 and 90 µm fluorescent polystyrene spheres (3–3 000 particles mL−1). Additionally, we investigated how developmental stages and a co-exposure to natural particles (e.g., food) modulate microplastic ingestion. All species ingested microplastics in a concentration-dependent manner with Daphnia magna consuming up to 6 180 particles h−1, followed by Chironomus riparius (226 particles h−1), Physella acuta (118 particles h−1), Gammarus pulex (10 particles h−1) and Lumbriculus variegatus (8 particles h−1). D. magna did not ingest 90 µm microplastics whereas the other species preferred larger microplastics over 1 µm in size. In C. riparius and D. magna, size preference depended on the life stage with larger specimens ingesting more and larger microplastics. The presence of natural particles generally reduced the microplastics uptake. Our results demonstrate that freshwater invertebrates have the capacity to ingest microplastics. However, the quantity of uptake depends on their feeding type and morphology as well as on the availability of microplastics.
Von Natur aus, so Döblin, kannte das Epische in seiner "unbegrenzten Form" kein bestimmtes Ende. Realität, Traum und Phantasie waren noch nicht voneinander geschieden; berichtet wurden "Elementarsituationen des menschlichen Daseins" in "immer neuen Abwandlungen", in der "Serienarbeit" der mündlichen und kollektiven Erzählungen und Nacherzählungen, im Grunde der "Wahrheit" ohne Begründung. Auf Einladung des Germanistikprofessors Julius Petersen hielt Döblin am 10. Dezember 1928 seinen Vortrag "Der Bau des epischen Werks" im Auditorium Maximum der Berliner Friedrich-Wilhelms-Universität. Darin erstellt er ein Programm zur Erneuerung des Romans unter den Bedingungen der modernen Kollektiverfahrungen von Masse, Technik und medialer Öffentlichkeit, in Verbindung mit den Wissensbeständen von Medizin, Psychiatrie und Soziologie und deren "Resonanz", wie er in seiner ganz persönlichen Universalschrift 'Unser Dasein' von 1933 schrieb, seiner letzten in Deutschland vor dem Exil erschienenen Publikation. Die Literatur hätte die Aufgabe, die neu entstandene Wirklichkeit zu "durchstoßen", das Menschenmögliche, auch die destruktiven Energien zur Sprache zu bringen: im Produktionsprozess eines als "dynamisches Netzwerk" zu begreifenden und plastisch zu gestaltenden Weltganzen, der Dinge und Vorgänge mit den in ihnen wirkenden Kräften. Die Vitalisierung und Elementarisierung der Sprache sollte den Ursprung des Epischen wiedergewinnen und die vorherrschende Repräsentationslogik der medialen Vermittlung außer Kraft setzen: "Das Buch ist der Tod der wirklichen Sprache."
Biogenesis of mitochondrial cytochrome c oxidase (COX) is a complex process involving the coordinate expression and assembly of numerous subunits (SU) of dual genetic origin. Moreover, several auxiliary factors are required to recruit and insert the redox-active metal compounds, which in most cases are buried in their protein scaffold deep inside the membrane. Here we used a combination of gel electrophoresis and pull-down assay techniques in conjunction with immunostaining as well as complexome profiling to identify and analyze the composition of assembly intermediates in solubilized membranes of the bacterium Paracoccus denitrificans. Our results show that the central SUI passes through at least three intermediate complexes with distinct subunit and cofactor composition before formation of the holoenzyme and its subsequent integration into supercomplexes. We propose a model for COX biogenesis in which maturation of newly translated COX SUI is initially assisted by CtaG, a chaperone implicated in CuB site metallation, followed by the interaction with the heme chaperone Surf1c to populate the redox-active metal-heme centers in SUI. Only then the remaining smaller subunits are recruited to form the mature enzyme which ultimately associates with respiratory complexes I and III into supercomplexes.
In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.
Aesthetic perception and judgement are not merely cognitive processes, but also involve feelings. Therefore, the empirical study of these experiences requires conceptualization and measurement of aesthetic emotions. Despite the long-standing interest in such emotions, we still lack an assessment tool to capture the broad range of emotions that occur in response to the perceived aesthetic appeal of stimuli. Elicitors of aesthetic emotions are not limited to the arts in the strict sense, but extend to design, built environments, and nature. In this article, we describe the development of a questionnaire that is applicable across many of these domains: the Aesthetic Emotions Scale (Aesthemos). Drawing on theoretical accounts of aesthetic emotions and an extensive review of extant measures of aesthetic emotions within specific domains such as music, literature, film, painting, advertisements, design, and architecture, we propose a framework for studying aesthetic emotions. The Aesthemos, which is based on this framework, contains 21 subscales with two items each, that are designed to assess the emotional signature of responses to stimuli’s perceived aesthetic appeal in a highly differentiated manner. These scales cover prototypical aesthetic emotions (e.g., the feeling of beauty, being moved, fascination, and awe), epistemic emotions (e.g., interest and insight), and emotions indicative of amusement (humor and joy). In addition, the Aesthemos subscales capture both the activating (energy and vitality) and the calming (relaxation) effects of aesthetic experiences, as well as negative emotions that may contribute to aesthetic displeasure (e.g., the feeling of ugliness, boredom, and confusion).
Background: The Objective Structured Clinical Examination (OSCE) is increasingly used at medical schools to assess practical competencies. To compare the outcomes of students at different medical schools, we introduced standardized OSCE stations with identical checklists.
Methods: We investigated examiner bias at standardized OSCE stations for knee- and shoulder-joint examinations, which were implemented into the surgical OSCE at five different medical schools. The checklists for the assessment consisted of part A for knowledge and performance of the skill and part B for communication and interaction with the patient. At each medical faculty, one reference examiner also scored independently to the local examiner. The scores from both examiners were compared and analysed for inter-rater reliability and correlation with the level of clinical experience. Possible gender bias was also evaluated.
Results: In part A of the checklist, local examiners graded students higher compared to the reference examiner; in part B of the checklist, there was no trend to the findings. The inter-rater reliability was weak, and the scoring correlated only weakly with the examiner’s level of experience. Female examiners rated generally higher, but male examiners scored significantly higher if the examinee was female.
Conclusions: These findings of examiner effects, even in standardized situations, may influence outcome even when students perform equally well. Examiners need to be made aware of these biases prior to examining.
In my paper I claim that methodology inspired by postcolonial theory not only unearths how Western international institutions perpetuate hegemonic truth claims, but that at the same time engaging in a “learning to learn from below” might sense irritations within these truth claims which can open up spaces to think beyond truth in a sense of a justice to come. (Derrida 2002) Since the (mis)understanding of knowledge production as truth finding is constitutive of both, the scientific and the legal discourse, the engagement in such research accordingly has the potential to unfold a twofold deconstructive force...
Was ist ein geographisches Bild? Darauf hat sicher jeder eine Antwort: Beim einen poppen im Kopf zunächst die Urlaubsfotos von der finnischen Schären-Küste oder aus Paris auf, die andere denkt an Satellitenaufnahmen des schwindenden Eisrandes der Arktis im GEO-Magazin oder an Claudia Kleinerts Wetterkarte in den Tagesthemen. Auf den ersten Blick scheint klar: alles Bilder, alles irgendwie geographisch.
Objective: Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression.
Methods: Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with (n = 20, 41.7%) or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS) integrated left ventricular vent in our retrospective single centre trial.
Results: Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14), bridge to transplant in 10.4% (n = 5) and bridge to recovery in 8.3% (n = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent). Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival.
Conclusion: ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.
Wer sich auf Spurensuche nach den Anfängen der modernen Sachliteratur für Kinder und Jugendliche begeben will, muss den Blick auf Strategien und Konzepte der Wissensvermittlung in der Literatur der Frühen Neuzeit richten. In der Zeit des 16. bis 18. Jahrhunderts entstand ausgehend von Innovationen der Pädagogik und Didaktik eine Wissen vermittelnde Kinder- und Jugendliteratur eigener Art. Die Methodik der Darstellung und adressatenspezifischen Zurichtung des Wissens in diesen Kinder- und Jugendbüchern akzentuiert zwar primär den omnipräsenten pädagogisch-didaktischen Anteil der Wissensvermittlung, lässt jedoch auch eine vornehmlich emblematisch-bildliche sowie eine wortbasierte, verbale Anschaulichkeit der Gestaltungsweise zu. Innovative Formen der Anschaulichkeit rücken den Zweck der Belehrung der Zöglinge in den Kontext einer kinder- und jugendorientierten Ästhetik der Wissensvermittlung. Diese dadurch entstehenden Formen der Anschaulichkeit sind es, die als Narrative in Bild und Wort erscheinen. Sie bilden das Inszenierte und das Ästhetische der Wissensvermittlung. ...
Der Zeitabschnitt zwischen 1815 bis 1848, der demokratisch-republikanische Vorfrühling, wird in der Literaturhistorik kontrovers gesehen und diskutiert. Denn zum Einen war da das Sich Reibende der Menschen an Verhältnissen, die zusehends durch ökonomischen Druck gekennzeichnet waren, und ihr daraus resultierendes Unwohlsein. Es gab etwas Gärendes, eine Unzufriedenheit, die sich Bahn brechen sollte und zur politischen Eruption von 1848 führte. Da war aber auch das Streben derjenigen, die man im Nachhinein unter dem Begriff Biedermeier subsumiert hat, nach der ländlichen Idylle und dem Rückzug ins Private. Es gab den Wunsch von vielen, der Kapitalismus, der am Horizont aufzuziehen begann, möge einen selbst noch verschonen, es möge einen Ausweg geben, und so reagiert auch der literarische Klassiker jener Epoche, Georg Büchners Figur Lenz, der einem wirklichen Menschen nachempfunden ist, verstört auf die zunehmende Kapitalisierung seiner Umgebung. Auch Lenz versucht, sich ihr zu entziehen, und Generationen von Schulkindern wurden Zeugen seiner Flucht ins Gebirge, die vergeblich bleiben musste. Lenz blieb letztlich nichts, als sich in eine Welt zu fügen, die nicht die seine war. Von nun an tat er: "[...] Alles wie es die Andern taten, es war aber eine entsetzliche Leere in ihm, er fühlte keine Angst mehr, kein Verlangen; sein Dasein war ihm eine notwendige Last. – So lebte er hin."
Gab es wirklich keine Möglichkeit, sich aus einer Entwicklung zu retten, die ein anderer Klassiker aus jenen Jahren folgendermaßen beschrieben hat: "Die Bourgeoisie," das sagen Karl Marx und Friedrich Engels im "Manifest der Kommunistischen Partei", das erstmals zu Beginn des revolutionären Jahres 1848 erschienen ist, "wo sie zur Herrschaft gekommen, hat alle feudalen, patriarchalischen, idyllischen Verhältnisse zerstört. Sie hat die buntscheckigen Feudalbande, die den Menschen an seinen natürlichen Vorgesetzten knüpften, unbarmherzig zerrissen und kein anderes Band zwischen Mensch und Mensch übriggelassen als das nackte Interesse, als die gefühllose bare Zahlung."
Welche Optionen gab es, auf "das nackte Interesse" und "die gefühllose bare Zahlung" zu reagieren? Georg Büchner hatte für die Revolte optiert und hatte sie gelebt, er hatte fliehen müssen und war jung verstorben. Andere versuchten, sich einen privaten Rückzugsort zu schaffen. Die Französin Louise Michel jedoch stand für einen dritten Weg, der allein der ihre war: Sie wollte sterben. Und ihren Todeswunsch hat sie mit großem Pathos verkündet.
Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic processes are involved in disease development and may be affected by sphingolipids. However, details about early-stage pathophysiological mechanisms and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed in skin tissue. Nevertheless, almost nothing is known about the dermatological contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the pathological changes seen in SSc. In this study, we observed a novel effect of S1P5 on the inflammatory processes during low-dose bleomycin (BLM)-induced fibrogenesis in murine skin. By comparing 2-week-treated skin areas of wild-type (WT) and S1P5-deficient mice, we found that S1P5 is important for the transcriptional upregulation of the Th2 characteristic transcription factor GATA-3 under treatment-induced inflammatory conditions, while T-bet (Th1) and FoxP3 (Treg) mRNA expression was regulated independently of S1P5. Additionally, treatment caused a regulation of S1P receptor 1 and S1P receptor 3 mRNA as well as a regulation of long-chain ceramide profiles, which both differ significantly between the genotypes. Despite S1P5-dependent differences regarding inflammatory processes, similar macroscopic evidence of fibrosis was detected in the skin histology of WT and S1P5-deficient mice after 4 weeks of subcutaneous BLM treatment. However, at the earlier 2-week point in time, the mRNA data of pro-collagen type 1 and SMAD7 indicate a pro-fibrotic S1P5 contribution in the applied SSc mouse model. In conclusion, we propose that S1P5 plays a role as a novel modulator during the early phase of BLM-caused fibrogenesis in murine skin. An immediate relationship between dermal S1P5 expression and fibrotic processes leading to skin alterations, such as formative for SSc pathogenesis, is indicated but should be studied more profound in further investigations. Therefore, this study is an initial step in understanding the role of S1P5-mediated effects during early stages of fibrogenesis, which may encourage the ongoing search for new therapeutic options for SSc patients.
Invasive fungal infections are still an important cause of morbidity and mortality in immunocompromised patients such as patients suffering from hematological malignancies or patients undergoing hematopoietic stem cell transplantion. In addition, other populations such as human immunodeficiency virus-patients are at higher risk for invasive fungal infection. Despite the availability of new antifungal compounds and better supportive care measures, the fatality rate of invasive fungal infection remained unacceptably high. It is therefore of major interest to improve our understanding of the host–pathogen interaction to develop new therapeutic approaches such as adoptive immunotherapy. As experimental methodologies have improved and we now better understand the complex network of the immune system, the insight in the interaction of the host with the fungus has significantly increased. It has become clear that host resistance to fungal infections is not only associated with strong innate immunity but that adaptive immunity (e.g., T cells) also plays an important role. The antifungal activity of natural killer (NK) cells has been underestimated for a long time. In vitro studies demonstrated that NK cells from murine and human origin are able to attack fungi of different genera and species. NK cells exhibit not only a direct antifungal activity via cytotoxic molecules but also an indirect antifungal activity via cytokines. However, it has been show that fungi exert immunosuppressive effects on NK cells. Whereas clinical data are scarce, animal models have clearly demonstrated that NK cells play an important role in the host response against invasive fungal infections. In this review, we summarize clinical data as well as results from in vitro and animal studies on the impact of NK cells on fungal pathogens.
Impact of human mesenchymal stromal cells on antifungal host response against Aspergillus fumigatus
(2017)
Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with Aspergillus fumigatus and the impact of MSCs on different arms of the anti-Aspergillus host response in vitro. Although A. fumigatus hyphae increase mRNA levels of IL6 in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte Aspergillus conidia, but phagocytosis of conidia is not associated with an alteration of the cytokine production by MSCs. In addition, human MSCs do not affect activation and function of A. fumigatus specific CD4+ T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our in vitro data indicate that administration of human MSCs is not associated with a negative impact on the host response against A. fumigatus and that the fungus does not stimulate MSCs to increase the release of those cytokines which play a central role in the pathophysiology of GvHD.
In situ single particle analysis of ice particle residuals (IPRs) and out-of-cloud aerosol particles was conducted by means of laser ablation mass spectrometry during the intensive INUIT-JFJ/CLACE campaign at the high alpine research station Jungfraujoch (3580 m a.s.l.) in January–February 2013. During the 4-week campaign more than 70 000 out-of-cloud aerosol particles and 595 IPRs were analyzed covering a particle size diameter range from 100 nm to 3 µm. The IPRs were sampled during 273 h while the station was covered by mixed-phase clouds at ambient temperatures between −27 and −6 °C. The identification of particle types is based on laboratory studies of different types of biological, mineral and anthropogenic aerosol particles. The outcome of these laboratory studies was characteristic marker peaks for each investigated particle type. These marker peaks were applied to the field data. In the sampled IPRs we identified a larger number fraction of primary aerosol particles, like soil dust (13 ± 5 %) and minerals (11 ± 5 %), in comparison to out-of-cloud aerosol particles (2.4 ± 0.4 and 0.4 ± 0.1 %, respectively). Additionally, anthropogenic aerosol particles, such as particles from industrial emissions and lead-containing particles, were found to be more abundant in the IPRs than in the out-of-cloud aerosol. In the out-of-cloud aerosol we identified a large fraction of aged particles (31 ± 5 %), including organic material and secondary inorganics, whereas this particle type was much less abundant (2.7 ± 1.3 %) in the IPRs. In a selected subset of the data where a direct comparison between out-of-cloud aerosol particles and IPRs in air masses with similar origin was possible, a pronounced enhancement of biological particles was found in the IPRs.
Steilhänge der Mittelgebirge weisen eine kleinräumige standörtliche Vielfalt auf und wurden aufgrund ihrer exponierten Lage bereits frühzeitig durch den Menschen u. a. als Befestigungsanlage genutzt. Daraus resultierte häufig eine hohe floristische und vegetationskundliche Diversität mit hohem Naturschutzwert. Durch Umwelt- und Nutzungsveränderungen hat sich aber auch an diesen Standorten in den letzten Jahrzehnten ein starker Wandel vollzogen. Durch Auswertung alter Florenlisten und Vegetationsaufnahmen und durch aktuelle Erhebungen wollen wir die Vegetationszusammensetzung der Lengder Burg, eines Steilhangs auf Unterem Muschelkalk im südlichen Göttinger Wald (Süd-Niedersachsen, Deutschland), und ihre Veränderung aufzeigen und Rückschlüsse für die zukünftige Behandlung ziehen. Dazu wurden Angaben zur Gefäßpflanzenflora aus dem Zeitraum 1950 bis 1995 mit einer aktuellen floristischen Kartierung des Gesamtgebiets von 2016 verglichen. Die Vegetationszusammensetzung wurde anhand von 37 Vegetationsaufnahmen aus dem früheren Zeitraum harakterisiert. 29 dieser Flächen wurden 2009 bis 2016 erneut aufgenommen. Räumliche und zeitliche Unterschiede in der Diversität und Artenzusammensetzung wurden hinsichtlich verschiedener standörtlicher Parameter und ökologischer Artengruppen analysiert.
Die Vegetation lässt sich zwei Gruppen zuordnen: 1. Das Carici-Fagetum und seine Kontaktgesellschaften an südlich und westlich exponierten Steilhängen. 2. Das Hordelymo-Fagetum mit verschiedenen Ausbildungen auf dem Plateau und an flacheren Süd- und Nordhangbereichen. Im Carici-Fagetum ist ein deutlicher Diversitätsverlust und eine Zunahme in der Dominanzstruktur der Krautschicht zu erkennen, der im Vergleich der Aufnahmezeiträume auf eine zunehmende Homogenisierung der Vegetation hinweist. Zurückgegangen sind dabei besonders die typischen Kenn- und Trennarten dieser Waldgesellschaft bei gleichzeitiger Zunahme der Buche in der Verjüngung. Im Hordelymo-Fagetum bewirkt neben Gehölzen in der Strauch- und Krautschicht vor allem die Zunahme von Allium ursinum eine homogenere Artenzusammensetzung, jedoch ohne Diversitätsverlust. Neben Stickstoffeinträgen, dem Klimawandel sowie einem reduzierten Rehwild-Verbiss bedingt besonders der Nutzungswandel diese Veränderungen. Vor allem im Carici-Fagetum wirkte sich der Übergang zwischen früherer Nieder- und Mittelwald-Nutzung mit Waldweide über eine fast 100jährige Hochwald-Nutzung bis zum jetzigen Schutzwald stark aus. Gleichwohl weisen die steilen Hänge weiterhin einen hohen Anteil an Rote-Liste-Arten auf und tragen wesentlich zur hohen Biodiversität des Gebiets bei. Veränderungen in der Vegetation der Lengder Burg spiegeln die Veränderungen im Göttinger Wald insgesamt wider. Kleinflächige Offenhaltungsmaßnahmen zur Erhaltung wertvoller floristischer Elemente sind teilweise erfolgreich. Kleinwüchsige, lichtbedürftige Magerkeitszeiger verschwinden jedoch zunehmend aus den sich entwickelnden, hochwüchsigen Stauden-Säumen. In den benachbarten, unbewirtschafteten Hangbuchenwäldern sorgt die fehlende Nutzung nach Jahrhunderten der Auflichtung und Aushagerung für eine Sukzession in Richtung mesophilen Kalkbuchenwalds.
Three-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid’s size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 105 to 1 × 106 cells/mm3. Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture.
Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis
(2017)
Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR1640 mice, and EAE in Lpar2 -/- mice. Serum LPAs were reduced in MS and EAE whereas spinal cord LPAs in TCR1640 mice increased during the ‘symptom-free’ intervals, i.e. on resolution of inflammation during recovery hence possibly pointing to positive effects of brain LPAs during remyelination as suggested in previous studies. Peripheral LPAs mildly re-raised during relapses but further dropped in refractory relapses. The peripheral loss led to a redistribution of immune cells from the spleen to the spinal cord, suggesting defects of lymphocyte homing. In support, LPAR2 positive T-cells were reduced in EAE and the disease was intensified in Lpar2 deficient mice. Further, treatment with an LPAR2 agonist reduced clinical signs of relapsing-remitting EAE suggesting that the LPAR2 agonist partially compensated the endogenous loss of LPAs and implicating LPA signaling as a novel treatment approach.
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores. Analysis of EAE models, treatment schedules, single and total doses, routes of administration, and onset of treatment from pre-immunization up to 35 days after immunization revealed high heterogeneity. Total doses ranged from 0.1 to 360 mg/kg for observation times of up to 35 days after immunization. About half of experiments (142/253) used total doses of 10–70 mg/kg. Employing this range, we tested anti-Itga4 as a reference mAb at varying schedules and got no, mild or substantial EAE-score reductions, depending on the mouse strain and onset of the treatment. The result agrees with the range of outcomes achieved in 10 reported anti-Itga4 experiments. Studies comparing low and high doses of various mAbs or early vs. late onset of treatment did not reveal dose-effect or timing-effect associations, with a tendency towards better outcomes with preventive treatments starting within the first week after immunization. The systematic comparison allows for extraction of some “common” design characteristics, which may be helpful to further assess the efficacy of mAbs and role of specific targets in preclinical models of multiple sclerosis.
Die aus Amerika stammende, neophytische Kolumbianische Zwergwasserlinse Wolffia columbiana wurde in Europa erstmals im Jahr 2013 in Deutschland und den Niederlanden nachgewiesen. Daraufhin wurden weitere 11 Freilandvorkommen von Wolffia aus Deutschland (Nordrhein-Westfalen, Hessen und Rheinland-Pfalz), den Niederlanden und Polen überprüft. Bei 10 der insgesamt 13 untersuchten Proben handelte es sich um Wolffia columbiana, darunter alle 8 bislang untersuchten Vorkommen aus Deutschland. Lediglich bei 3 Freilandproben aus den Niederlanden und Polen handelte es sich um die einheimische Wolffia arrhiza. Der Neophyt scheint also durchaus weiter verbreitet zu sein als gedacht. Die Unterscheidung beider Arten ist nicht ganz leicht, die Unterscheidungsmerkmale werden vorgestellt. Die Vorkommen von Wolffia in Europa sollten überprüft werden, um zu klären, wie viele Vorkommen von Wolffia arrhiza es überhaupt noch gibt, und bei wie vielen Vorkommen es sich tatsächlich um die neophytische Wolffia columbiana oder andere neophytische Wolffia-Arten handelt.
In cancer medicine, particularly in drug research and development, structural changes in professionalism can be observed as examples. This field is characterized by a strong tension between social expectations concerning the control of existential risks to health, on the one hand, and strong commercial interests of a shareholder value-driven industry, on the other hand. Based on a qualitative empirical analysis, two subfields within the field of cancer medicine are reconstructed. One of these subfields—colon cancer therapy—could be interpreted as representing a renewal of the knowledge-power nexus. The pattern of the other subfield—brain tumour research—refers to a much more vulnerable professionalism. Both fields are characterized by development in professional work, which could be described with the hybridization concept. Therefore, the contrast between the two empirical examples presented still challenges the theoretical interpretation of contemporary professionalism.
Editorial
(2017)
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic, Th17-derived cytokine thought to critically contribute to the pathogenesis of diverse autoimmune diseases, including rheumatoid arthritis and psoriasis. Treatment with monoclonal antibodies that block GM-CSF activity is associated with favorable therapeutic effects in patients with rheumatoid arthritis. We evaluated the role of GM-CSF as a potential target for therapeutic interference in psoriasis using a combined pharmacologic and genetic approach and the mouse model of imiquimod-induced psoriasiform dermatitis (IMQPD). Neutralization of murine GM-CSF by an anti-GM-CSF antibody ameliorated IMQPD. In contrast, genetic deficiency in GM-CSF did not alter the course of IMQPD, suggesting the existence of mechanisms compensating for chronic, but not acute, absence of GM-CSF. Further investigation uncovered an alternative pathogenic pathway for IMQPD in the absence of GM-CSF characterized by an expanded plasmacytoid dendritic cell population and release of IFNα and IL-22. This pathway was not activated in wild-type mice during short-term anti-GM-CSF treatment. Our investigations support the potential value of GM-CSF as a therapeutic target in psoriatic disease. The discovery of an alternative pathogenic pathway for psoriasiform dermatitis in the permanent absence of GM-CSF, however, suggests the need for monitoring during therapeutic use of long-term GM-CSF blockade.
Ice nucleating particles over the eastern mediterranean measured by unmanned aircraft systems
(2017)
During an intensive field campaign on aerosol, clouds, and ice nucleation in the Eastern Mediterranean in April 2016, we measured the abundance of ice nucleating particles (INPs) in the lower troposphere from unmanned aircraft systems (UASs). Aerosol samples were collected by miniaturized electrostatic precipitators onboard the UASs at altitudes up to 2.5 km. The number of INPs in these samples, which are active in the deposition and condensation modes at temperatures from −20 to −30 °C, were analyzed immediately after collection on site using the ice nucleus counter FRIDGE (FRankfurt Ice nucleation Deposition freezinG Experiment). During the 1-month campaign, we encountered a series of Saharan dust plumes that traveled at several kilometers' altitude. Here we present INP data from 42 individual flights, together with aerosol number concentrations, observations of lidar backscattering, dust concentrations derived by the dust transport model DREAM (Dust Regional Atmospheric Model), and results from scanning electron microscopy. The effect of the dust plumes is reflected by the coincidence of INPs with the particulate matter (PM), the lidar signal, and the predicted dust mass of the model. This suggests that mineral dust or a constituent related to dust was a major contributor to the ice nucleating properties of the aerosol. Peak concentrations of above 100 INPs std L−1 were measured at −30 °C. The INP concentration in elevated plumes was on average a factor of 10 higher than at ground level. Since desert dust is transported for long distances over wide areas of the globe predominantly at several kilometers' altitude, we conclude that INP measurements at ground level may be of limited significance for the situation at the level of cloud formation.
A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany.
The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany.
This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n = 976) received BTA therapy. In 2014–2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6–70.8), 38 months (95% CI 29.4–44.2) to 28 months (95% CI 24.2–31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively.
We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.
NADPH oxidases of the Nox family are important enzymatic sources of reactive oxygen species (ROS) in the cardiovascular system. Of the 7 members of the Nox family, at least three depend for their activation on specific cytosolic proteins. These are p47phox and its homologue NoxO1 and p67phox and its homologue NoxA1. Also the Rho-GTPase Rac is important but as this protein has many additional functions, it will not be covered here. The Nox1 enzyme is preferentially activated by the combination of NoxO1 with NoxA1, whereas Nox2 gains highest activity with p47phox together with p67phox. As p47phox, different to NoxO1 contains an auto inhibitory region it has to be phosphorylated prior to complex formation. In the cardio-vascular system, all cytosolic Nox proteins are expressed but the evidence for their contribution to ROS production is not well established. Most data have been collected for p47phox, whereas NoxA1 has basically not yet been studied. In this article the specific aspects of cytosolic Nox proteins in the cardiovascular system with respect to Nox activation, their expression and their importance will be reviewed. Finally, it will be discussed whether cytosolic Nox proteins are suitable pharmacological targets to tamper with vascular ROS production.
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression. Whole exome and transcriptome sequencing of the four tumor lines and a germline control were applied to identify expressed somatic single nucleotide substitutions (SNS), insertions and deletions (indels). Candidate peptides encoded by these variants and predicted to bind to the patient’s HLA class I alleles were synthesized and tested for recognition by autologous mixed lymphocyte-tumor cell cultures (MLTCs). Peptides from four mutated proteins, HERPUD1G161S, INSIG1S238F, MMS22LS437F and PRDM10S1050F, were recognized by MLTC responders and MLTC-derived T cell clones restricted by HLA-A*24:02 or HLA-B*15:01. Intracellular peptide processing was verified with transfectants. All four neoantigens could only be targeted on the cell line generated during early stage III disease. HLA loss variants of any kind were uniformly resistant. These findings corroborate that, although neoantigens represent attractive therapeutic targets, they also contribute to the process of cancer immunoediting as a serious limitation to specific T cell immunotherapy.
According to a proposal by 't Hooft, information loss introduced by constraints in certain classical dissipative systems may lead to quantization. This scheme can be realized within the Bateman model of two coupled oscillators, one damped and one accelerated. In this paper we analyze the links of this approach to effective Hamiltonians where the environmental degrees of freedom do not appear explicitly but their effect leads to the same friction force appearing in the Bateman model. In particular, it is shown that by imposing constraints, the Bateman Hamiltonian can be transformed into an effective one expressed in expanding coordinates. This one can be transformed via a canonical transformation into Caldirola and Kanai's effective Hamiltonian that can be linked to the conventional system-plus-reservoir approach, for example, in a form used by Caldeira and Leggett.
Der französische Frühsozialist Pierre-Joseph Proudhon (1809-1865) gilt unumstritten als der "Vater der Anarchie". Auf ihn geht die positive Umdeutung des Begriffs "Anarchismus" zurück. Sein Einfluss und seine Bedeutung für die Entstehung des sog. wissenschaftlichen Sozialismus und auf die anarchistische Bewegung in Deutschland sind von nicht zu unterschätzender Bedeutung. Er hat darüber hinaus, mehr noch als seine Vorläufer Claude-Henri Saint-Simon und Charles Fourier, größeren Einfluss auf den deutschen Diskurs über Sozialismus gehabt. Der Historiker Max Nettlau erklärte über seine deutsche Rezeption:
Proudhon wurde in Deutschland sehr beachtet, wo damals die radikale Philosophie um Arnold Ruge und Ludwig Feuerbach sich nach einer folgerichtigen Weiterentwicklung auf allen Gebieten sehnte, also dem die Theologie negierenden philosophischen Radikalismus, den den Staat negierenden politischen Radikalismus und die bestehenden Eigentumsverhältnisse negierenden ökonomischen Radikalismus zur Seite zu setzen bereit war.
Als Zeitraum für die Untersuchung seiner Rezeption in Deutschland bietet sich das Vierteljahrhundert von 1840, dem Erscheinungsjahr von Proudhons Studie „Qu’est-ce que la propriété?“, bis zum Jahr 1865, in dem er starb, an.
We present first data on centrality dependent K+, K− and ϕ production in Au+Au collisions at a kinetic beam energy of 1.23A GeV measured with HADES. We observe no significant increase of the K+/K− and ϕ/K− multiplicity ratios with centrality of the collision. The measured ϕ/K− ratio is found to be larger than results at higher energies. The significant ϕ feed-down contribution to the K− yield substantially softens the measured transverse mass spectrum of K−, explaining its lower observed effective temperature in comparison to the one of K+.
The present article encompasses the bibliography of Prof. Horst Schuller, researcher, literature Historian and translator.
This article refers to a number of translators, who translate from German to Romanian and also to the bibliography of their translations Georg Aescht, Theochar Alexi, Verona Bratesch (Brateş), Maria Dima, Sextil-Iosif Puşcariu, Daniel Friedrich Rhein, Arnold Roth, Christian W. Schenk
The RNA-chaperone Hfq catalyses the annealing of bacterial small RNAs (sRNAs) with target mRNAs to regulate gene expression in response to environmental stimuli. Hfq acts on a diverse set of sRNA-mRNA pairs using a variety of different molecular mechanisms. Here, we present an unusual crystal structure showing two Hfq-RNA complexes interacting via their bound RNA molecules. The structure contains two Hfq6:A18 RNA assemblies positioned face-to-face, with the RNA molecules turned towards each other and connected via interdigitating base stacking interactions at the center. Biochemical data further confirm the observed interaction, and indicate that RNA-mediated contacts occur between Hfq-RNA complexes with various (ARN)X motif containing RNA sequences in vitro, including the stress response regulator OxyS and its target, fhlA. A systematic computational survey also shows that phylogenetically conserved (ARN)X motifs are present in a subset of sRNAs, some of which share similar modular architectures. We hypothesise that Hfq can co-opt RNA-RNA base stacking, an unanticipated structural trick, to promote the interaction of (ARN)X motif containing sRNAs with target mRNAs on a "speed-dating" fashion, thereby supporting their regulatory function.
Green tea (GT) and green tea extracts (GTE) have been postulated to decrease cancer incidence. In vitro results indicate a possible effect; however, epidemiological data do not support cancer chemoprevention. We have performed a PubMED literature search for green tea consumption and the correlation to the common tumor types lung, colorectal, breast, prostate, esophageal and gastric cancer, with cohorts from both Western and Asian countries. We additionally included selected mechanistical studies for a possible mode of action. The comparability between studies was limited due to major differences in study outlines; a meta analysis was thus not possible and studies were evaluated individually. Only for breast cancer could a possible small protective effect be seen in Asian and Western cohorts, whereas for esophagus and stomach cancer, green tea increased the cancer incidence, possibly due to heat stress. No effect was found for colonic/colorectal and prostatic cancer in any country, for lung cancer Chinese studies found a protective effect, but not studies from outside China. Epidemiological studies thus do not support a cancer protective effect. GT as an indicator of as yet undefined parameters in lifestyle, environment and/or ethnicity may explain some of the observed differences between China and other countries.
Das im zweijährigen Turnus stattfindende International Symposium on Place Names (ISPN) wurde unter Leitung von Prof. Herman Breyer ausgerichtet.
In zahlreichen Vorträgen wurde herausgearbeitet, welche hohe Bedeutung die Namengebung für Straßen, Schulen und andere öffentliche Einrichtungen für die Identitätsstiftung besitzen kann. Ein weiterer Aspekt, der in vielfältiger Weise diskutiert wurde, ist die Relevanz von Toponymen als Teil des historischen Erbes.
The mammalian thalamocortical system generates intrinsic activity reflecting different states of excitability, arising from changes in the membrane potentials of underlying neuronal networks. Fluctuations between these states occur spontaneously, regularly, and frequently throughout awake periods and influence stimulus encoding, information processing, and neuronal and behavioral responses. Changes of pupil size have recently been identified as a reliable marker of underlying neuronal membrane potential and thus can encode associated network state changes in rodent cortex. This suggests that pupillometry, a ubiquitous measure of pupil dilation in cognitive neuroscience, could be used as an index for network state fluctuations also for human brain signals. Considering this variable may explain task-independent variance in neuronal and behavioral signals that were previously disregarded as noise.
Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
(2017)
Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.
Am 25. und 26. November 2016 fand am Germanistischen Institut der Westfälischen Wilhelms-Universität die vom Autor dieses Berichts organisierte Tagung „Historische Wortbildung. Theorie – Methoden – Perspektiven“ statt. Dabei sollte vor allem die diachrone Wortbildungsforschung zum Deutschen Berücksichtigung finden, eine Forschungsrichtung also, die nach wie vor eine Forschungslücke darstellt. Die heute zur Verfügung stehenden synchronen Beschreibungen der Wortbildung früherer Sprachstufen sowie die Digitalisierung historischer Textbestände und deren Implementierung in komplexe Datenbanken (z. B. des Deutschen Textarchivs2, des Altdeutschen Referenzkorpus3, etc.) bieten der diachron-historischen Wortbildungsforschung neue Möglichkeiten, die es nun zu nutzen gilt.
Can variances of latent variables be scaled in such a way that they correspond to eigenvalues?
(2017)
The paper reports an investigation of whether sums of squared factor loadings obtained in confirmatory factor analysis correspond to eigenvalues of exploratory factor analysis. The sum of squared factor loadings reflects the variance of the corresponding latent variable if the variance parameter of the confirmatory factor model is set equal to one. Hence, the computation of the sum implies a specific type of scaling of the variance. While the investigation of the theoretical foundations suggested the expected correspondence between sums of squared factor loadings and eigenvalues, the necessity of procedural specifications in the application, as for example the estimation method, revealed external influences on the outcome. A simulation study was conducted that demonstrated the possibility of exact correspondence if the same estimation method was applied. However, in the majority of realized specifications the estimates showed similar sizes but no correspondence.
Microtubule-targeting agents (MTAs) are the most widely used chemotherapeutic drugs. Pretubulysin (PT), a biosynthetic precursor of the myxobacterial tubulysins, was recently identified as a novel MTA. Besides its strong anti-tumoral activities, PT attenuates tumor angiogenesis, exerts anti-vascular actions on tumor vessels and decreases cancer metastasis formation in vivo. The aim of the present study was to analyze the impact of PT on the interaction of endothelial and tumor cells in vitro to gain insights into the mechanism underlying its anti-metastatic effect. The influence of PT on tumor cell adhesion and transmigration onto/through the endothelium as well as its influence on cell adhesion molecules and the chemokine system CXCL12/CXCR4 was investigated. Treatment of human endothelial cells with PT increased the adhesion of breast cancer cells to the endothelial monolayer, whereas their transmigration through the endothelium was strongly reduced. Interestingly, the PT-induced upregulation of ICAM-1, VCAM-1 and CXCL12 were dispensable for the PT-evoked tumor cell adhesion. Tumor cells preferred to adhere to collagen exposed within PT-triggered endothelial gaps via β1-integrins on the tumor cell surface. Taken together, our study provides, at least in part, an explanation for the anti-metastatic potential of PT.
FinTech as enabler of entrepreneurship and growth in the EU : interview with Joachim Schwerin
(2017)
A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.
Previous studies detected an influence of urban characteristics on song traits in passerine birds, that is, song adjustments to ambient noise in urban areas. Several studies already described the effect of weather conditions on the behavior of birds, but not the effect on song traits. We investigate, if song trait variability changes along a continuous urbanity gradient in Frankfurt am Main, Germany. We examined, for the first time on a larger scale, the influence of weather on song parameters. We made song recordings of three common passerine species: the blue and great tit (Cyanistes caeruleus (Linnaeus, 1758) and Parus major Linnaeus, 1758) and the European blackbird (Turdus merula Linnaeus, 1758). We measured different song traits and performed statistical analyses and modeling on a variety of variables—among them urbanity and weather parameters. Remarkably, we found only few cases of a significant influence of urbanity parameters on song traits. The influence of weather parameters (air pressure, atmospheric humidity, air and soil temperatures) on song traits was highly significant. Birds in Frankfurt face high noise pollution and might show different adaptations to high noise levels. The song trait variability of the investigated species is affected more by weather conditions than by urban characteristics in Frankfurt. However, the three species react differently to specific weather parameters. Smaller species seem to be more affected by weather than larger species.
Organized by Sabine Schulte im Walde (University of Stuttgart) and Eva Smolka (University of Konstanz) as part of the 39th Annual Conference of the German Linguistic Society (DGfS) held at the Saarland University in Saarbrücken, Germany, the workshop aimed “to shed light on the interaction of constituent properties and compound transparency across languages and disciplines integrating linguistic, psycholinguistic, corpus-based and computational studies”. The workshop brought together researchers from linguistics, psycholinguistics, and natural language processing and comprised 11 contributed talks, framed by two invited talks by Gary Libben and Marco Marelli. Most of the slides are available from the workshop’s homepage at “http://www.ims.uni-stuttgart.de/events/dgfs-mwe-17/program.html”.
TechQuartier to boost the start-up scene in Frankfurt am Main : interview with Sebastian Schäfer
(2017)
Interview with Sebastian Schäfer, Managing Director TechQuartier, Frankfurt
A randomised, double-blind, placebo-controlled trial of trichuris suis ova in active crohn's disease
(2017)
BACKGROUND AND AIMS To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD].
METHODS Adults with active CD [n = 252] randomly received six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250, TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion, with 4 weeks' follow-up. Primary endpoint was the rate of clinical remission [Crohn's Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12 or withdrawal. Secondary endpoints included the course of clinical remission, rate of clinical response, change in CDAI, change in markers of inflammation, mucosal healing, and Physician's Global Assessment.
RESULTS Clinical remission at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns.
CONCLUSIONS Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose-dependent immunological response, but no TSO dose showed a clinically relevant effect over placebo for induction of clinical remission or response in mildly-to-moderately active, ileocolonic CD.
Neurleptic drugs, e.g., aripiprazole, targeting the dopamine D2S and D3 receptors (D2SR and D3R) in the central nervous system are widely used in the treatment of several psychotic and neurodegenerative diseases. Therefore, a new series of benzothiazole-based ligands (3-20) was synthesized by applying the bioisosteric approach derived from the selective D3Rs ligand BP-897 (1) and its structurally related benz[d]imidazole derivative (2). Herein, introduction of the benzothiazole moiety was well tolerated by D2SR and D3R binding sites leading to antagonist affinities in the low nanomolar concentration range at both receptor subtypes. However, all novel compounds showed lower antagonist affinity to D3R when compared to that of 1. Further exploration of different substitution patterns at the benzothiazole heterocycle and the basic 4-phenylpiperazine resulted in the discovery of high dually acting D2SR and D3R ligands. Moreover, the methoxy substitution at 2-position of 4-phenylpiperazine resulted in significantly (22-fold) increased D2SR binding affinity as compared to the parent ligand 1, and improved physicochemical and drug-likeness properties of ligands 3-11. However, the latter structural modifications failed to improve the drug-able properties in ligands having un-substituted 4-phenylpiperazine analogs (12-20). Accordingly, compound 9 showed in addition to high dual affinity at the D2SR and D3R [Ki (hD2SR) = 2.8 ± 0.8 nM; Ki (hD3R) = 3.0 ± 1.6 nM], promising clogS, clogP, LE (hD2SR, hD3R), LipE (hD2SR, hD3R), and drug-likeness score values of −4.7, 4.2, (0.4, 0.4), (4.4, 4.3), and 0.7, respectively. Also, the deaminated analog 10 [Ki (hD2SR) = 3.2 ± 0.4 nM; Ki (hD3R) = 8.5 ± 2.2 nM] revealed clogS, clogP, LE (hD2SR, hD3R), LipE (hD2SR, hD3R) and drug-likeness score values of −4.7, 4.2, (0.4, 0.4), (3.9, 3.5), and 0.4, respectively. The results observed for the newly developed benzothiazole-based ligands 3-20 provide clues for the diversity in structure activity relationships (SARs) at the D2SR and D3R subtypes.
In evidence-based weight-loss programs weight regain is common after an initial weight reduction. Eating slowly significantly lowers meal energy intake and hunger ratings. Despite this knowledge, obese individuals do not implement this behaviour. We, thus tested the hypothesis of changing eating behaviour with an intra-oral medical device leading to constant weight reduction in overweight and obesity.
Six obese patients (6 men, age 56 ± 14, BMI 29 ± 2 kg / m2) with increased CVRF profile were included in this prospective study. All patients had been treated for obesity during the last 10 years in a single centre and had at least 3 frustrate evidence-based diets. Patients received a novel non-invasive intra-oral medical device to slow eating time. Further advice included not to count calories, to avoid any other form of diet, to take their time with their meals, and to eat whatever they liked.
This device was used only during meals for the first 4 to 8 weeks for a total of 88 [20–160] hours. Follow-up period was 23 [15–38] months. During this period, patients lost 11% [5–20%] (p<0.001) of their initial weight. At 12 months, all patients had lost >5%, and 67% (4/6) achieved a >10% bodyweight loss. In the course of the study, altered eating patterns were observed. There were no complications with the medical device. Of note, all patients continued to lose weight after the initial intervention period (p<0.001) and none of them had weight regain.
With this medical device, overweight and obese patients with a history of previously frustrating attempts to lose weight achieved a significant and sustained weight loss over two years. These results warrant the ongoing prospective randomised controlled trial to prove concept and mechanism of action.
Oxygenation-sensitive spin relaxation time T2′ and relaxation rate R2′ (1/T2′) are presumed to be markers of the cerebral oxygen extraction fraction (OEF) in acute ischemic stroke. In this study, we investigate the relationship of T2′/R2′ with dynamic susceptibility contrast-based relative cerebral blood flow (rCBF) in acute ischemic stroke to assess their plausibility as surrogate markers of the ischemic penumbra. Twenty-one consecutive patients with internal carotid artery and/or middle cerebral artery occlusion were studied at 3.0 T. A physiological model of the cerebral vasculature (VM) was used to process PWI raw data in addition to a conventional deconvolution technique. T2′, R2′, and rCBF values were extracted from the ischemic core and hypoperfused areas. Within hypoperfused tissue, no correlation was found between deconvolved rCBF and T2′ (r = −0.05, p = 0.788), or R2′ (r = 0.039, p = 0.836). In contrast, we found a strong positive correlation with T2′ (r = 0.444, p = 0.006) and negative correlation with R2′ (r = −0.494, p = 0.0025) for rCBFVM, indicating increasing OEF with decreasing CBF and that rCBF based on the vascular model may be more closely related to metabolic disturbances. Further research to refine and validate these techniques may enable their use as MRI-based surrogate markers of the ischemic penumbra for selecting stroke patients for interventional treatment strategies.
Einen schönen Einstieg in "Rechtspluralismus" bietet ein jüdischer Witz: Zum Rabbi kam ein Mann und lamentierte über seine Ehefrau. Sie erziehe die Kinder falsch und kümmere sich zu wenig um den Haushalt. Sie koche nicht gut und sonst allerlei gelinge ihr ebenfalls nicht. Daraufhin dachte der Rabbi kurz nach und sagte: "Ja, ja, sicher, Du hast Recht." Am Tag darauf kam die Frau zum Rabbi und beschwerte sich heftig über ihren Ehemann. Dieser kümmere sich zu Hause um gar nichts, liege nur faul herum und sonst sei auch nichts mit ihm anzufangen. Da dachte der Rabbi wieder kurz nach und antwortete: "Ja, ja, Du hast Recht." Beiden Gesprächen wohnte der Schüler des Rabbis bei. Dieser wunderte sich nun und fragte den Rabbi in vorwurfsvollem Ton: "Du kannst nicht geben Recht dem Einen und dann der Anderen. Das geht nicht, dass beide Recht haben." Da dachte der Rabbi wieder nach und sprach: "Ja, ja, Du hast auch Recht." ...
QCD matter physics at FAIR
(2017)
The Compressed Baryonic Matter (CBM) experiment will be one of the major scientific pillars of the future Facility for Antiproton and Ion Research (FAIR) in Darmstadt. The goal of the CBM research program is to explore the QCD phase diagram in the region of high baryon densities using high-energy nucleus-nucleus collisions. This includes the study of the equation-of-state of nuclear matter at neutron star core densities, and the search for the deconfinement and chiral phase transitions. The CBM detector is designed to measure rare diagnostic probes such as hadrons including multi-strange (anti-) hyperons, lepton pairs, and charmed particles with unprecedented precision and statistics. Most of these particles will be studied for the first time in the FAIR energy range. In order to achieve the required precision, the measurements will be performed at very high reaction rates of 1 to 10 MHz. This requires very fast and radiation-hard detectors, a novel data read-out and analysis concept based on free streaming front-end electronics, and a high-performance computing cluster for online event selection. The status of FAIR and the physics program of the proposed CBM experiment will be discussed.
The phenomenon of jet quenching provides essential information about the properties of hot and dense matter created in ultra-relativistic heavy-ion collisions. Recent results from experiments at the Large Hadron Collider (LHC) show evidence for an unexpectedly similar suppression of both light and heavy flavor jets. Furthermore, the role of radiative energy loss of heavy quarks is still under active discussion within the theoretical community. By employing the parton cascade Boltzmann Approach to Multi-Parton Scatterings (BAMPS), which numerically solves the 3+1 D Boltzmann equation both for light and heavy flavor partons, we calculate the nuclear modification factor of inclusive and b-tagged reconstructed jets in 0–10% central sLHC=2.76ATeV Pb + Pb collisions. Based on perturbative QCD cross sections we find a suppression of both light and heavy flavor jets. While the inclusive jets are slightly too strong suppressed within Bamps in comparison with data, both elastic + radiative and only elastic interactions lead to a realistic b-tagged jet suppression. To further investigate light and heavy flavor energy loss we predict the R dependence of inclusive and b-tagged jet suppression. Furthermore, we propose the medium modification of b-tagged jet shapes as an observable for discriminating between different heavy quark energy loss scenarios.
The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different pyramidal cell types in motor cortex due to TMS. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to calculate activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also shows differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of cortical pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical pyramidal cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.
The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different pyramidal cell types in motor cortex due to TMS. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to calculate activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also shows differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of cortical pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical pyramidal cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.
Box C/D snoRNAs are known to guide site-specific ribose methylation of ribosomal RNA. Here, we demonstrate a novel and unexpected role for box C/D snoRNAs in guiding 18S rRNA acetylation in yeast. Our results demonstrate, for the first time, that the acetylation of two cytosine residues in 18S rRNA catalyzed by Kre33 is guided by two orphan box C/D snoRNAs–snR4 and snR45 –not known to be involved in methylation in yeast. We identified Kre33 binding sites on these snoRNAs as well as on the 18S rRNA, and demonstrate that both snR4 and snR45 establish extended bipartite complementarity around the cytosines targeted for acetylation, similar to pseudouridylation pocket formation by the H/ACA snoRNPs. We show that base pairing between these snoRNAs and 18S rRNA requires the putative helicase activity of Kre33, which is also needed to aid early pre-rRNA processing. Compared to yeast, the number of orphan box C/D snoRNAs in higher eukaryotes is much larger and we hypothesize that several of these may be involved in base-modifications.
Coccolithophores are an abundant phytoplankton group that exhibit remarkable diversity in their biology, ecology and calcitic exoskeletons (coccospheres). Their extensive fossil record is a testament to their important biogeochemical role and is a valuable archive of biotic responses to environmental change stretching back over 200 million years. However, to realise the full potential of this archive for (palaeo-)biology and biogeochemistry requires an understanding of the physiological processes that underpin coccosphere architecture. Using culturing experiments on four modern coccolithophore species (Calcidiscus leptoporus, Calcidiscus quadriperforatus, Helicosphaera carteri and Coccolithus braarudii) from three long-lived families, we investigate how coccosphere architecture responds to shifts from exponential (rapid cell division) to stationary (slowed cell division) growth phases as cell physiology reacts to nutrient depletion. These experiments reveal statistical differences in coccosphere size and the number of coccoliths per cell between these two growth phases, specifically that cells in exponential-phase growth are typically smaller with fewer coccoliths, whereas cells experiencing growth-limiting nutrient depletion have larger coccosphere sizes and greater numbers of coccoliths per cell. Although the exact numbers are species-specific, these growth-phase shifts in coccosphere geometry demonstrate that the core physiological responses of cells to nutrient depletion result in increased coccosphere sizes and coccoliths per cell across four different coccolithophore families (Calcidiscaceae, Coccolithaceae, Isochrysidaceae and Helicosphaeraceae), a representative diversity of this phytoplankton group. Building on this, the direct comparison of coccosphere geometries in modern and fossil coccolithophores enables a proxy for growth phase to be developed that can be used to investigate growth responses to environmental change throughout their long evolutionary history. Our data also show that changes in growth rate and coccoliths per cell associated with growth-phase shifts can substantially alter cellular calcite production. Coccosphere geometry is therefore a valuable tool for accessing growth information in the fossil record, providing unprecedented insights into the response of species to environmental change and the potential biogeochemical consequences.
We review the recent developments of analytic solutions in transverse magneto-hydrodynamics under Bjorken expansion. It is found that the time dependence of magnetic fields can either increase or reduce the energy density depending on the decay exponent of magnetic fields. Moreover, perturbative solutions under weak magnetic fields with spatial inhomogeneity results in transverse flow, where the directions of flow also depend on the decay exponent of magnetic fields in time.
We study the charmonium coherent photoproduction and hadroproduction consistently with modifications from both cold and hot nuclear matters. The strong electromagnetic fields from fast moving nucleus interact with the other target nucleus, producing abundant charmonium in the extremely low transverse momentum region pT<0.1 GeV/c. This results in significative enhancement of J/ψ nuclear modification factor in semi-central and peripheral collisions. In the middle pT region such as pT<3∼5 GeV/c, J/ψ final yield is dominated by the combination process of single charm and anti-charm quarks moving in the deconfined matter, c+c¯→J/ψ+g. In the higher pT region, J/ψ production are mainly from parton initial hard scatterings at the beginning of nucleus–nucleus collisions and decay of B hadrons. We include all of these production mechanisms and explain the experimental data well in different colliding centralities and transverse momentum regions.
Mobilization of hematopoietic stem cells (HSCs) from the bone marrow to the peripheral blood is a complex mechanism that involves adhesive and chemotactic interactions of HSCs as well as their bone marrow microenvironment. In addition to a number of non-genetic factors, genetic susceptibilities also contribute to the mobilization outcome. Identification of genetic factors associated with HSC yield is important to better understand the mechanism behind HSC mobilization. In the present study, we enrolled 148 Korean participants (56 healthy donors and 92 patients) undergoing HSC mobilization for allogeneic or autologous HSC transplantation. Among a total of 53 polymorphisms in 33 candidate genes, one polymorphism (rs11264422) in relaxin/insulin-like family peptide receptor 4 (RXFP4) gene was significantly associated with a higher HSC yield after mobilization in Koreans. However, in a set of 101 Europeans, no association was found between circulating CD34+ cell counts and rs11264422 genotype. Therefore, we suggest that the ethnic differences in subjects’ genetic background may be related to HSC mobilization. In conclusion, the relaxin—relaxin receptor axis may play an important role in HSC mobilization. We believe that the results of the current study could provide new insights for therapies that use relaxin and HSC populations, as well as a better understanding of HSC regulation and mobilization at the molecular level.
No presente artigo analisamos a ideia de solidariedade na teoria da justiça de Axel Honneth. Honneth em sua obra atualiza a teoria hegeliana da eticidade e concebe a existência de esferas de liberdade, sendo que uma delas é a liberdade social, na qual se situam relações pessoais, mercado e instituições políticas. Em O Direito da Liberdade Honneth desenvolve uma teoria em que busca analisar os problemas de desenvolvimento da democracia nas sociedades contemporâneas, e erige a solidariedade como um dos pressupostos normativos para a construção de uma democracia virtuosa, ancorada na participação cidadã.
O presente estudo tem como objetivo investigar a ideia de reconhecimento jurídico na teoria de Axel Honneth, o que se dará mediante análise da obra Luta por Reconhecimento. Honneth, ancorado nas teorias de Hegel e Mead, estabelece o papel do direito como esfera de reconhecimento individual e seu potencial de asseguramento do autorrespeito. Empreende-se uma reconstrução da teoria honnethiana no atinente aos papéis desempenhados pelo direito na teoria da Luta por Reconhecimento de Axel Honneth, para em seguida, a partir da leitura que o autor desenvolve da teoria de Thomas Marshall, analisar o papel desempenhado pelos direitos subjetivos fundamentais como medium de sedimentação e ampliação de novas formas de reconhecimento e cidadania.
Information theory provides a formal framework within which information processing and its disorders can be described. However, information theory has rarely been applied to modeling aspects of the cognitive neuroscience of schizophrenia. The goal of this article is to highlight the benefits of an approach based on information theory, including its recent extensions, for understanding several disrupted neural goal functions as well as related cognitive and symptomatic phenomena in schizophrenia. We begin by demonstrating that foundational concepts from information theory—such as Shannon information, entropy, data compression, block coding, and strategies to increase the signal-to-noise ratio—can be used to provide novel understandings of cognitive impairments in schizophrenia and metrics to evaluate their integrity. We then describe more recent developments in information theory, including the concepts of infomax, coherent infomax, and coding with synergy, to demonstrate how these can be used to develop computational models of schizophrenia-related failures in the tuning of sensory neurons, gain control, perceptual organization, thought organization, selective attention, context processing, predictive coding, and cognitive control. Throughout, we demonstrate how disordered mechanisms may explain both perceptual/cognitive changes and symptom emergence in schizophrenia. Finally, we demonstrate that there is consistency between some information-theoretic concepts and recent discoveries in neurobiology, especially involving the existence of distinct sites for the accumulation of driving input and contextual information prior to their interaction. This convergence can be used to guide future theory, experiment, and treatment development.
Bromus racemosus L. is a rather rare grass species of moist meadows. It has strongly decreased in the course of the 20th century due to intensification of agricultural grassland management, and is therefore included in Red Lists of several European countries. Its winter annual life-cycle is remarkable for a species of permanent grasslands.
The aim of this study is to determine the habitat preference and optimal management of B. racemosus in the Netherlands and surrounding countries. Vegetation, soil and hydrological data from 28 sites in the Netherlands have been compared with B. racemosus cover, and with vegetation data from surrounding countries. The results indicate that B. racemosus is characteristic of Molinio-Arrhenatheretea meadows with good mineralisation and aftermath grazing. The optimum lies in grasslands of the alliance Alopecurion pratensis (Deschampsion cespitosae), but the species ranges from wetter Calthion palustris meadows to drier Arrhenatherion elatioris and Cynosurion cristati grasslands. It prefers intermediate nutrient levels and hydrological conditions (mesic sites), but within this range the highest cover is found in relatively nutrient rich and dry sites. Because of the absence of a seedbank and a low dispersal capability, B. racemosus is vulnerable to changes in grassland management. A management of mowing after 15 June and aftermath grazing is most suitable, since it enables fruit ripening and the maintenance of an open sward, needed for germination and development. The risk of extinction is likely to be higher in flat polders than in floodplain sites with natural relief, where the species may shift between belts in different years.
Im Jahr 1926 erschien in der 'Revista de Occidente', einer von José Ortega y Gasset in Madrid herausgegebenen Zeitschrift mit kulturpolitischer und philosophischer Ausrichtung, eine merkwürdige Publikation unter dem rätselhaften Titel "Cancionero apócrifo de Abel Martín. Recopilación y estudio de Juan de Mairena." Auf den ersten Blick scheint es so, als fungiere Antonio Machado hier lediglich als Herausgeber einer von Juan de Mairena kompilierten Sammlung, welche wiederum der Autorschaft eines Abel Martín zugeschrieben wird. Trotz der rätselhaften doppelten Herausgeberfiktion hatte das damalige Lesepublikum offenbar keine Probleme damit, Antonio Machado als den eigentlichen Autor der genannten "apokryphen" Prosa- und Gedichttexte zu identifizieren. Denn die Namen Juan de Mairena und Abel Martín bezeichnen nicht etwa reale Dichterpersönlichkeiten der damaligen Epoche oder der spanischen Literatur- geschichte, sondern sie sind – wie die damaligen Leser durch Ausschlussverfahren selbst erraten konnten – Konstrukte von Machados Phantasie, fiktive Autorprojektionen, deren Erfindung und Gestaltung er mit erstaunlichem gedanklichen Aufwand und Akribie betrieben hatte. Abel Martín und sein 'Schüler' Mairena gehören zu einem ganzen Spektrum von imaginierten Dichtern und Philosophen, deren fingierte Werke ihr Erfinder Machado als "apokryph" bezeichnete. Die bemerkenswerte Praktik, eigene Hervorbringungen, Lyrik und Prosa, nicht unter dem eigenen Namen zu publizieren, sondern einem Kreis fingierter Autorpersönlichkeiten zuzuordnen, hebt sich von dem gewöhnlichen Gebrauch von Pseudonymen, von künstlerischen Decknamen, deutlich ab. Zumal der Autor in jenem Zeitraum in den 1910er und 1920er Jahren keineswegs mehr ein Unbekannter war.
Dem Apokryphen einen Themenschwerpunkt im Rahmen einer komparatistischen Zeitschrift zu widmen ist eine Entscheidung, die auf den ersten Blick erstaunen mag. Ist doch das Wort "apokryph" ein in der heutigen Alltagssprache wenig geläufiger Begriff, der, auf das Register der Theologie verweisend, speziellen Fragen und fachwissenschaftlichen Debatten der Religionsgeschichte vorbehalten zu sein scheint. Wenn wir gleichwohl Begriff und Phänomen des Apokryphen als Schwerpunktthema des Jahrbuchs 'Komparatistik' zur Diskussion stellen wollen, so deshalb, weil der damit angesprochene Sachverhalt von Prozessen der Auswahl, Marginalisierung und Ausgrenzung im Rahmen kultureller und textueller Überlieferung ein Problemfeld markiert, das im Bereich der Literaturgeschichte vielfältige Resonanzen und Parallelen findet und in systematischer Hinsicht über Verfahren und Mechanismen literarischer Traditionsbildung Aufschluss zu geben verspricht. Weit davon entfernt, nur ein spezialdiskursives Sonderphänomen zu sein, erweist sich das Apokryphe bei näherem Hinsehen als eine Figur, an der sich grundsätzliche Fragen der Formation von Text- und Wissensbeständen, der literarischen Autorität und Kanonbildung beobachten lassen. Apokryphe Texte, so ließe sich in einer vorläufigen, im Folgenden noch zu präzisierenden Beschreibung formulieren, sind Texte, die sich am Rande der großen Traditionen religiöser und kultureller Bewegungen situieren. Es sind Texte oder Textensembles, die es, wie sich im Rückblick bemerken lässt, nicht geschafft haben, in das Inventar jener Schriften aufgenommen zu werden, die als anerkannt, bewahrenswert oder wahr gelten. Als Einstieg bietet es sich an, zunächst von den Bedeutungsdimensionen des Ausdrucks apokryph auszugehen, die dieser im Kontext der religionsgeschichtlichen Tradition angenommen hat und der für das heute übliche Verständnis des Begriffs bestimmend ist. Der religiöse bzw. theologische Begriffsgebrauch greift auf das altgriechische Wort ἀπόκρυφος (apókryphos) zurück, um dieses vor allem in einer seiner beiden Bedeutungsschichten zum Einsatz zu bringen, nämlich als Bezeichnung eines Gegenstands bzw. Textes, der als 'unecht', 'zweifelhaft', 'nicht-authentisch' zu gelten habe. Der Begriff apokryph führt hier also eine Unterscheidung ein zwischen dem, was als gesichert, gültig und autorisiert anzusehen ist und dem, was solche Geltung zu besitzen nicht oder nur unter dem Vorbehalt des Zweifelhaften beanspruchen kann. Bei dem Begriffspaar gültig vs. apokryph haben wir es also mit einer Figur der Verknappung zu tun, die ein gegebenes Textensemble oder eine kulturelle Überlieferung einem mitunter radikalen Verfahren der Auswahl und Reduktion unterzieht.
The yeast bc1 complex (complex III) and cytochrome oxidase (complex IV) are mosaics of core subunits encoded by the mitochondrial genome and additional nuclear-encoded proteins imported from the cytosol. Both complexes build in the mitochondrial inner membrane various supramolecular assemblies. The formation of the individual complexes and their supercomplexes depends on the activity of dedicated assembly factors. We identified a so far uncharacterized mitochondrial protein (open reading frame YDR381C-A) as an important assembly factor for complex III, complex IV, and their supercomplexes. Therefore, we named this protein Cox interacting (Coi) 1. Deletion of COI1 results in decreased respiratory growth, reduced membrane potential, and hampered respiration, as well as slow fermentative growth at low temperature. In addition, coi1Δ cells harbour reduced steady-state levels of subunits of complexes III and IV as well as of the assembled complexes and supercomplexes. Interaction of Coi1 with respiratory chain subunits seems transient, as it appears to be a stoichiometric subunit neither of complex III nor of complex IV. Collectively, this work identifies a novel protein that plays a role in the assembly of the mitochondrial respiratory chain.
Most event studies rely on cumulative abnormal returns, measured as percentage changes in stock prices, as their dependent variable. Stock price reflects the value of the operating business plus non-operating assets minus debt. Yet, many events, in particular in marketing, only influence the value of the operating business, but not non-operating assets and debt. For these cases, the authors argue that the cumulative abnormal return on the operating business, defined as the ratio between the cumulative abnormal return on stock price and the firm-specific leverage effect, is a more appropriate dependent variable. Ignoring the differences in firm-specific leverage effects inflates the impact of observations pertaining to firms with large debt and deflates those pertaining to firms with large non-operating assets. Observations of firms with high debt receive several times the weight attributed to firms with low debt. A simulation study and the reanalysis of three previously published marketing event studies shows that ignoring the firm-specific leverage effects influences an event study's results in unpredictable ways.
The physical housing environment is important to facilitate activities of daily living (ADL) for older people. A hindering environment may lead to ADL dependence and thus increase the need for home services, which is individually restricting and a growing societal burden. This study presents simulations of policy changes with regard to housing accessibility that estimates the potential impact specifically on instrumental activities of daily living (I-ADL), usage of home services, and related costs. The models integrate empirical data to test the hypothesis that a policy providing funding to remove the five most severe environmental barriers in the homes of older people who are at risk of developing dependence in I-ADL, can maintain independence and reduce the need for home services. In addition to official statistics from state agencies in Sweden and Germany, we utilized published results from the ENABLE-AGE and other scientific studies to generate the simulations. The simulations predicted that new policies that remove potentially hindering housing features would improve I-ADL performance among older people and reduce the need for home services. Our findings suggest that a policy change can contribute to positive effects with regard to I-ADL independence among older people and to a reduction of societal burden.
Vegetation patterns of floodplain forests are highly variable across different habitats in European regions. Their plant communities have been well described from the phytosociological point of view, but plant species richness and composition patterns and their underlying environmental factors are still insufficiently known. Sixty-one vegetation plots of black alder-dominated floodplain forests were sampled in central Slovakia in order to find main environmental predictors affecting floristic diversity of their vegetation. For each vegetation plot with a constant size (400m2), vascular plant species and a set of topographic, climatic, soil physical and chemical characteristics were recorded. A generalized linear model was applied to explain relevance of environmental factors on changes of species richness, whereas the relationship between species composition and explanatory variables was tested using ordination methods. Main gradients of species compositional variation were soil moisture, light, elevation and soil chemistry-related variables. Vascular species richness of plots varied between 19 and 59 (mean 38). Herb-layer species richness was positively related to the soil pH, stream power index and negatively to the concentration of soil iron. These linear trends were accompanied by a hump-shaped response to sand content and a U-shaped response to elevation.
Sex differences in the relationship between conduct disorder and cortical structure in adolescents
(2017)
Objective: Previous studies have reported reduced cortical thickness and surface area and altered gyrification in frontal and temporal regions in adolescents with conduct disorder (CD). Although there is evidence that the clinical phenotype of CD differs between males and females, no studies have examined whether such sex differences extend to cortical and subcortical structure.
Method: As part of a European multisite study (FemNAT-CD), structural magnetic resonance imaging (MRI) data were collected from 48 female and 48 male participants with CD and from 104 sex-, age-, and pubertal-status−matched controls (14–18 years of age). Data were analyzed using surface-based morphometry, testing for effects of sex, diagnosis, and sex-by-diagnosis interactions, while controlling for age, IQ, scan site, and total gray matter volume.
Results: CD was associated with cortical thinning and higher gyrification in ventromedial prefrontal cortex in both sexes. Males with CD showed lower, and females with CD showed higher, supramarginal gyrus cortical thickness compared with controls. Relative to controls, males with CD showed higher gyrification and surface area in superior frontal gyrus, whereas the opposite pattern was seen in females. There were no effects of diagnosis or sex-by-diagnosis interactions on subcortical volumes. Results are discussed with regard to attention-deficit/hyperactivity disorder, depression, and substance abuse comorbidity, medication use, handedness, and CD age of onset.
Conclusion: We found both similarities and differences between males and females in CD–cortical structure associations. This initial evidence that the pathophysiological basis of CD may be partly sex-specific highlights the need to consider sex in future neuroimaging studies and suggests that males and females may require different treatments.
The existence of individual variation in males' motivation to mate remains a conundrum as directional selection should favour high mating frequencies. Balancing selection resulting from (context-dependent) female mate choice could contribute to the maintenance of this behavioural polymorphism. In dichotomous choice tests, mosquitofish (Gambusia holbrooki) females preferred virtual males showing intermediate mating frequencies, reflecting females' tendencies to avoid harassment by highly sexually active males. When tested in the presence of a female shoal—which protects females from male harassment—focal females showed significantly stronger preferences for high sexual activity. A trade-off between (indirect) benefits and (direct) costs of mating with sexually active males probably explains context-dependent female mate choice, as costs depend on the social environment in which females choose their mates. No preference was observed when we tested virgin females, suggesting that the behavioural pattern described here is part of the learned behavioural repertoire of G. holbrooki females.
BACKGROUND: Time-limited, early-life exposures to institutional deprivation are associated with disorders in childhood, but it is unknown whether effects persist into adulthood. We used data from the English and Romanian Adoptees study to assess whether deprivation-associated adverse neurodevelopmental and mental health outcomes persist into young adulthood.
METHODS: The English and Romanian Adoptees study is a longitudinal, natural experiment investigation into the long-term outcomes of individuals who spent from soon after birth to up to 43 months in severe deprivation in Romanian institutions before being adopted into the UK. We used developmentally appropriate standard questionnaires, interviews completed by parents and adoptees, and direct measures of IQ to measure symptoms of autism spectrum disorder, inattention and overactivity, disinhibited social engagement, conduct or emotional problems, and cognitive impairment (IQ score <80) during childhood (ages 6, 11, and 15 years) and in young adulthood (22-25 years). For analysis, Romanian adoptees were split into those who spent less than 6 months in an institution and those who spent more than 6 months in an institution. We used a comparison group of UK adoptees who did not experience deprivation. We used mixed-effects regression models for ordered-categorical outcome variables to compare symptom levels and trends between groups.
FINDINGS: Romanian adoptees who experienced less than 6 months in an institution (n=67 at ages 6 years; n=50 at young adulthood) and UK controls (n=52 at age 6 years; n=39 at young adulthood) had similarly low levels of symptoms across most ages and outcomes. By contrast, Romanian adoptees exposed to more than 6 months in an institution (n=98 at ages 6 years; n=72 at young adulthood) had persistently higher rates than UK controls of symptoms of autism spectrum disorder, disinhibited social engagement, and inattention and overactivity through to young adulthood (pooled p<0·0001 for all). Cognitive impairment in the group who spent more than 6 months in an institution remitted from markedly higher rates at ages 6 years (p=0·0001) and 11 years (p=0·0016) compared with UK controls, to normal rates at young adulthood (p=0·76). By contrast, self-rated emotional symptoms showed a late-onset pattern with minimal differences versus UK controls at ages 11 years (p=0·0449) and 15 years (p=0·17), and then marked increases by young adulthood (p=0·0005), with similar effects seen for parent ratings. The high deprivation group also had a higher proportion of people with low educational achievement (p=0·0195), unemployment (p=0·0124), and mental health service use (p=0·0120, p=0·0032, and p=0·0003 for use when aged <11 years, 11-14 years, and 15-23 years, respectively) than the UK control group. A fifth (n=15) of individuals who spent more than 6 months in an institution were problem-free at all assessments.
INTERPRETATION: Notwithstanding the resilience shown by some adoptees and the adult remission of cognitive impairment, extended early deprivation was associated with long-term deleterious effects on wellbeing that seem insusceptible to years of nurturance and support in adoptive families.
FUNDING: Economic and Social Research Council, Medical Research Council, Department of Health, Jacobs Foundation, Nuffield Foundation.
Este artigo apresenta uma discussão sobre a obra recente de Axel Honneth. Começando por uma exposição de seu projeto teórico mais amplo, descrito em O direito da liberdade (2011) como uma teoria da justiça sociologicamente ancorada, o artigo demonstra como Honneth se move da ideia de uma luta por reconhecimento em direção à ideia de intersubjetividade institucional. Este movimento, porém, é acompanhado por críticas que vêm nesta passagem o abandono das ambições críticas de seu modelo e um compromisso reformista com a ordem capitalista de mercado. A fim de responder a estas objeções, Honneth propõe uma reatualização da ideia do socialismo (2015) a partir da noção de liberdade social, concluindo com uma distinção entre duas formas de luta por reconhecimento, uma interna e outra externa – e defendendo as vantagens da primeira.
From reciprocal recognition to a society that is properly 'social' : on Axel Honneth's recent work
(2017)
This paper addresses Axel Honneth's recent endeavors to defend his theory of justice, broadly described in Freedom's right (2011) as an analysis of society. The paper begins by exposing Honneth's model as a theory of institutional intersubjectivity rather than a theory of the struggle for recognition. This model, however, was subject to criticism due to its supposed acceptance of the capitalistic market economy as a social order. In order to defend it from such objections, Honneth (2016) exposes the normative core of socialist ideals as a version of social freedom. Finally, he presents a distinction between two forms of political intervention: an internal and an external struggle for recognition – and asserts the advantages of the former.
Auf Grundlage einer interviewbasierten Studie zu heterosexuellen Paaren, in denen die Frau das Haupteinkommen verdient, beschäftigt sich der Beitrag mit milieuspezifischen Bewältigungsmustern prekärer Beschäftigungsverhältnisse. Vor dem Hintergrund der Erosion des Ernährermodells werden dabei Transformationen von Männlichkeit in den Blick genommen. Es wird die These entwickelt, dass sich mit dem Selbstverständnis als "Künstler" im hochqualifizierten individualisierten Milieu des urbanen Raums ein spezifisches Bewältigungsmuster von Prekarität herausgebildet hat.
Correlation of lumbar lateral recess stenosis in magnetic resonance imaging and clinical symptoms
(2017)
Aim: To assess the correlation of lateral recess stenosis (LRS) of lumbar segments L4/5 and L5/S1 and the Oswestry Disability Index (ODI).
Methods: Nine hundred and twenty-seven patients with history of low back pain were included in this uncontrolled study. On magnetic resonance images (MRI) the lateral recesses (LR) at lumbar levels L4/5 and L5/S1 were evaluated and each nerve root was classified into a 4-point grading scale (Grade 0-3) as normal, not deviated, deviated or compressed. Patient symptoms and disability were assessed using ODI. The Spearman’s rank correlation coefficient was used for statistical analysis (P < 0.05).
Results: Approximately half of the LR revealed stenosis (grade 1-3; 52% at level L4/5 and 42% at level L5/S1) with 2.2% and 1.9% respectively reveal a nerve root compression. The ODI score ranged from 0%-91.11% with an arithmetic mean of 34.06% ± 16.89%. We observed a very weak statistically significant positive correlation between ODI and LRS at lumbar levels L4/5 and L5/S1, each bilaterally (L4/5 left: rho < 0.105, P < 0.01; L4/5 right: rho < 0.111, P < 0.01; L5/S1 left: rho 0.128, P < 0.01; L5/S1 right: rho < 0.157, P < 0.001).
Conclusion: Although MRI is the standard imaging tool for diagnosing lumbar spinal stenosis, this study showed only a weak correlation of LRS on MRI and clinical findings. This can be attributed to a number of reasons outlined in this study, underlining that imaging findings alone are not sufficient to establish a reliable diagnosis for patients with LRS.