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Increasing recognition of general practice is reflected in the growing number of university institutes devoted to the subject and Health Services Research (HSR) is flourishing as a result. In May 2015 the Institute of General Practice and Evidence-based Health Services Research, Medical University of Graz, initiated a survey of Styrian GPs. The aim of the survey was to determine the willingness to take part in HSR projects, to collect sociodemographic data from GPs who were interested and to identify factors affecting participation in research projects. Of the 1015 GPs who received the questionnaire, 142 (14%) responded and 135 (13%) were included in the analysis. Overall 106 (10%) GPs indicated their willingness to take part in research projects. Factors inhibiting participation were lack of time, administrative workload, and lack of assistance. Overall, 10% of Styrian GPs were willing to participate in research projects. Knowledge about the circumstances under which family doctors are prepared to participate in HSR projects will help in the planning of future projects.
The red yeast Xanthophyllomyces dendrorhous is an established platform for the synthesis of carotenoids. It was used for the generation of novel multi oxygenated carotenoid structures. This was achieved by a combinatorial approach starting with the selection of a β-carotene accumulating mutant, stepwise pathway engineering by integration of three microbial genes into the genome and finally the chemical reduction of the resulting 4,4’-diketo-nostoxanthin (2,3,2’,3’-tetrahydroxy-4,4’-diketo-β-carotene) and 4-keto-nostoxanthin (2,3,2’,3’-tetrahydroxy-4-monoketo-β-carotene). Both keto carotenoids and the resulting 4,4’-dihydroxy-nostoxanthin (2,3,4,2’,3’,4’-hexahydroxy-β-carotene) and 4-hydroxy-nostoxanthin (2,3,4,2’3’-pentahydroxy-β-carotene) were separated by high-performance liquid chromatography (HPLC) and analyzed by mass spectrometry. Their molecular masses and fragmentation patterns allowed the unequivocal identification of all four carotenoids.
Brain-derived neurotrophic factor (BDNF), an important neural growth factor, has gained growing interest in neuroscience, but many influencing physiological and analytical aspects still remain unclear. In this study we assessed the impact of storage time at room temperature, repeated freeze/thaw cycles, and storage at −80 °C up to 6 months on serum and ethylenediaminetetraacetic acid (EDTA)-plasma BDNF. Furthermore, we assessed correlations of serum and plasma BDNF concentrations in two independent sets of samples. Coefficients of variations (CVs) for serum BDNF concentrations were significantly lower than CVs of plasma concentrations (n = 245, p = 0.006). Mean serum and plasma concentrations at all analyzed time points remained within the acceptable change limit of the inter-assay precision as declared by the manufacturer. Serum and plasma BDNF concentrations correlated positively in both sets of samples and at all analyzed time points of the stability assessment (r = 0.455 to rs = 0.596; p < 0.004). In summary, when considering the acceptable change limit, BDNF was stable in serum and in EDTA-plasma up to 6 months. Due to a higher reliability, we suggest favoring serum over EDTA-plasma for future experiments assessing peripheral BDNF concentrations.
We present the black hole accretion code (BHAC), a new multidimensional general-relativistic magnetohydrodynamics module for the MPI-AMRVAC framework. BHAC has been designed to solve the equations of ideal general-relativistic magnetohydrodynamics in arbitrary spacetimes and exploits adaptive mesh refinement techniques with an efficient block-based approach. Several spacetimes have already been implemented and tested. We demonstrate the validity of BHAC by means of various one-, two-, and three-dimensional test problems, as well as through a close comparison with the HARM3D code in the case of a torus accreting onto a black hole. The convergence of a turbulent accretion scenario is investigated with several diagnostics and we find accretion rates and horizon-penetrating fluxes to be convergent to within a few percent when the problem is run in three dimensions. Our analysis also involves the study of the corresponding thermal synchrotron emission, which is performed by means of a new general-relativistic radiative transfer code, BHOSS. The resulting synthetic intensity maps of accretion onto black holes are found to be convergent with increasing resolution and are anticipated to play a crucial role in the interpretation of horizon-scale images resulting from upcoming radio observations of the source at the Galactic Center.
Studies investigating the prevalence, cause, and consequence of multiple sclerosis (MS) fatigue typically use single measures that implicitly assume symptom-stability over time, neglecting information about if, when, and why severity fluctuates. We aimed to examine the extent of moment-to-moment and day-to-day variability in fatigue in relapsing-remitting MS and healthy individuals, and identify daily life determinants of fluctuations. Over 4 weekdays, 76 participants (38 relapsing-remitting MS; 38 controls) recruited from multiple sites provided real-time self-reports six times daily (n = 1661 observations analyzed) measuring fatigue severity, stressors, mood, and physical exertion, and daily self-reports of sleep quality. Fatigue fluctuations were evident in both groups. Fatigue was highest in relapsing-remitting MS, typically peaking in late-afternoon. In controls, fatigue started lower and increased steadily until bedtime. Real-time stressors and negative mood were associated with increased fatigue, and positive mood with decreased fatigue in both groups. Increased fatigue was related to physical exertion in relapsing-remitting MS, and poorer sleep quality in controls. In relapsing-remitting MS, fatigue fluctuates substantially over time. Many daily life determinants of fluctuations are similar in relapsing-remitting MS and healthy individuals (stressors, mood) but physical exertion seems more relevant in relapsing-remitting MS and sleep quality most relevant in healthy individuals.
The outset of Joyce’s A Portrait of the Artist as a Young Man presents a stage of life and language that is commonly evoked and, at the same time, systematically avoided in autobiographies as well as theoretical approaches to language: infancy. This textual strategy refers back to Augustine’s Confessiones, one of the most canonical autobiographies, reading it as a mainstay for an unconventional hypothesis: Rather that understanding infancy as an early stage of, or even before, language, Joyce expounds that the condition called infancy – the openness for receiving language while being unable to master it – accompanies all speech, be it childlike or eloquent. The article analyses Joyce’s text as one instance of a general paradox of autobiographical writing: initial aphasia. Setting out with birth or infancy, autobiographical texts precede articulate discourse. In Joyce, this paradox appears as starting point for a poetical – rather than theoretical – thinking about language, and language acquisition.
Background: Multimorbidity is associated with negative effects both on people’s health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12 months, as compared with usual care.
Methods/Design: Design: pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65–74 years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3 months). Sample size: n = 400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle.
Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes.
Trial registration: Clinicaltrials.gov, NCT02866799
Multimorbilidad en medicina de familia y los principios Ariadne : un enfoque centrado en la persona
(2017)
La multimorbilidad, definida como la presencia de dos o más enfermedades crónicas en un mismo individuo, conlleva consecuencias negativas para la persona e importantes retos para los sistemas sanitarios. En atención primaria, donde recae esencialmente la atención de este grupo de pacientes, la consulta es más compleja que la de un paciente con una única enfermedad debido, entre otros, al hecho de tener que manejar mayor cantidad de información clínica, disponer de poca evidencia científica para abordar la multimorbilidad, y tener que coordinar la labor de múltiples profesionales para garantizar la continuidad asistencial. Además, para poder implementar correctamente los planes de tratamiento en estos pacientes es necesario un proceso de toma de decisiones compartida médico-paciente. Entre las distintas herramientas disponibles para apoyar dicho proceso, recientemente se ha desarrollado una dirigida específicamente a pacientes con multimorbilidad en atención primaria y que se describe en el presente artículo: los principios Ariadne.
Wenn der heilige Martin im frühen Mittelalter zum Hausheiligen der Karolinger und Merowinger avanciert und als Schlachtenhelfer angerufen wird, dann liegt das in seiner allgemeinen Anrufbarkeit als Heiliger begründet und dem Vertrauen in seine Wunderkraft, derer man sich durch seine Reliquien – allen voran die Mantelhälfte – versichern wollte, während es für die von ihm erhoffte Schlachtenhilfe "in seiner Lebensgeschichte keinen beweiskräftigen Rückhalt" gibt. Dass er selbst einst Soldat war, spielt dabei keinerlei Rolle – nicht einmal in einer jener seltsam schief anmutenden Übertragungen, die das Patronat eines Heiligen mit dessen Folterinstrument verknüpfen, so im Falle des Soldaten-Märtyrers Sebastian, der zum Patron der Bogenschützen wird, durch deren Pfeile er doch zu Tode kam. Allenfalls wäre von einer in der Latenz bleibenden ikonischen, auf Ähnlichkeit beruhenden, Zeichenrelation auszugehen, die im einstigen Soldaten und nunmehr spirituellen Gottesstreiter Martin ein kriegerisches Handeln im Namen Gottes vorgebildet sieht. Explizit gemacht wird ein solcher Zusammenhang aber nicht. Martin bleibt der wundertätige und barmherzige Mönchsbischof, sein "Streiten" bleibt metaphorisch und erinnert daran, dass in der christlichen Tradition Gewalt gerade kein Heilsweg ist.
Dieser Beitrag geht nun vor allem begrifflich-historischen Aspekten des Zusammenhangs von 'Sicherheit' und 'Unverfügbarkeit' nach, wobei ich historisch und konzeptuell vor allem an 'Sicherheit' interessiert bin. 'Unverfügbarkeit' oder 'Nichtverfügbarkeit' wird unterdessen in weiten Teilen heuristisch gebraucht, zum Zwecke der Zusammenschau bestimmter Phänomene.
The intercultural novel of Julya Rabinowich The Earth-eater is fed with complex motivs and intertextual allusions, shows the physical and psychological ruin of a migrant, forced by social conditions to sell her body to survive. Closely interwoven are memories of her childhood and her previous, bitter life. Rabinowich gives an insight into the hardened and thoroughly abysmal emotional world of her protagonist, who belongs to those who „get up and go on”, but also into the capitalist value system, which judges man according to his productive power. In the end, the novel leaves the reality plane and echoes into the surreal to signal the complete descent of the figure into madness and death. In order to better illustrate the psychosis caused by uprooting and abandonment, Julya Rabinowich makes bonds in the Jewish literary traditions.
Objectives: It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process.
Setting: In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed.
Results: This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition.
Conclusions: While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge.
Trial registration: number ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).
Retinal OFF bipolar cells show distinct connectivity patterns with photoreceptors in the wild-type mouse retina. Some types are cone-specific while others penetrate further through the outer plexiform layer (OPL) to contact rods in addition to cones. To explore dendritic stratification of OFF bipolar cells in the absence of rods, we made use of the ‘cone-full’ Nrl-/- mouse retina in which all photoreceptor precursor cells commit to a cone fate including those which would have become rods in wild-type retinas. The dendritic distribution of OFF bipolar cell types was investigated by confocal and electron microscopic imaging of immunolabeled tissue sections. The cells’ dendrites formed basal contacts with cone terminals and expressed the corresponding glutamate receptor subunits at those sites, indicating putative synapses. All of the four analyzed cell populations showed distinctive patterns of vertical dendritic invasion through the OPL. This disparate behavior of dendritic extension in an environment containing only cone terminals demonstrates type-dependent specificity for dendritic outgrowth in OFF bipolar cells: rod terminals are not required for inducing dendritic extension into distal areas of the OPL.
Background: Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement ‘hotspot’ loci. However, microdeletion burden not overlapping these regions or within different epilepsy subtypes has not been ascertained.
Objective: To decipher the role of microdeletions outside hotspots loci and risk assessment by epilepsy subtype.
Methods: We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1366 patients with genetic generalised epilepsy (GGE) in addition to two sets of additional unpublished genome-wide microdeletions found in 281 patients with rolandic epilepsy (RE) and 807 patients with adult focal epilepsy (AFE), totalling 2454 cases. Microdeletions were assessed in a combined and subtype-specific approaches against 6746 controls.
Results: When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted p=1.06×10−6,OR 1.89, 95% CI 1.51 to 2.35). Epilepsy subtype-specific analyses showed that hotspot microdeletions in the GGE subgroup contribute most of the overall signal (adjusted p=9.79×10−12, OR 7.45, 95% CI 4.20–13.5). Outside hotspots , microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted p=9.13×10−3,OR 2.85, 95% CI 1.62–4.94). No additional signal was observed for RE and AFE. Still, gene-content analysis identified known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes across epilepsy subtypes that were not deleted in controls.
Conclusions: Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor contribution in the aetiology of RE and AFE.
Size-resolved measurements of atmospheric aerosol and cloud condensation nuclei (CCN) concentrations and hygroscopicity were conducted at the remote Amazon Tall Tower Observatory (ATTO) in the central Amazon Basin over a full seasonal cycle (Mar 2014–Feb 2015). In a companion part 1 paper, we presented an in-depth CCN characterization based on annually as well as seasonally averaged time intervals and discuss different parametrization strategies to represent the Amazonian CCN cycling in modelling studies (M. Pöhlker et al., 2016b). The present part 2 study analyzes the aerosol and CCN variability in original time resolution and, thus, resolves aerosol advection and transformation for the following case studies, which represent the most characteristic states of the Amazonian atmosphere:
1. Near-pristine (NP) conditions, defined as the absence of detectable black carbon (< 0.01 µg m−3), showed their highest occurrence (up to 30 %) in the wet season (i.e., Mar–May). On average, the NP episodes are characterized by a bimodal aerosol size distribution (strong Aitken mode: DAit = 70 nm, NAit = ~ 200 cm−3 vs. weaker accumulation mode: Dacc = 170 nm, Nacc = ~ 60 cm−3), a mostly organic particle composition, and relatively low hygroscopicity levels (κAit = 0.12 vs. κacc = 0.18). The NP CCN efficiency spectrum shows that the CCN population is sensitive to changes in supersaturation (S) over a wide S range.
2. Long-range transport (LRT) conditions frequently mix Saharan dust, African combustion smoke, and sea spray aerosols into the Amazonian wet season atmosphere. The LRT episodes (i.e., Feb–Apr) are characterized by an accumulation mode dominated size distribution (DAit = 80 nm, NAit = 120 cm−3 vs. Dacc = 180 nm, Nacc = 300 cm−3), a clearly increased abundance of dust and salt compounds, and relatively high hygroscopicity levels (κAit = 0.18, κacc = 0.34). The LRT CCN efficiency spectrum shows that the CCN population is highly sensitive to changes in S in the low S regime.
3. Biomass burning (BB) conditions dominate the Amazonian dry season. A selected characteristic BB episode shows a very strong accumulation mode (DAit = 70 nm, NAit = ~ 140 cm−3 vs. Dacc = 170 nm, Nacc = ~ 3400 cm−3), particles with very high organic fractions (> 90 %), and correspondingly low hygroscopicity levels (κAit = 0.14, κacc = 0.17). The BB CCN efficiency spectrum shows that the CCN population is highly sensitive to changes in S in the low S regime.
4. Mixed pollution conditions show the superposition of African (i.e., volcanic) and Amazonian (i.e., biomass burning) aerosol emissions during the dry season. The African aerosols showed a broad monomodal distribution (D = 130 nm, N = ~ 1300 cm−3), with very high sulfate fractions (20 %), and correspondingly high hygroscopicity (κAit = 0.14, κacc = 0.22). This was superimposed by fresh smoke from nearby fires with one strong mode (D = 113 nm, Nacc = ~ 2800 cm−3), an organic-dominated aerosol, and sharply decreased hygroscopicity (κAit = 0.10, κacc = 0.20). These conditions underline the rapidly changing pollution regimes with clear impacts on the aerosol and CCN properties.
Overall, this study provides detailed insights into the CCN cycling in relation to aerosol-cloud interaction in the vulnerable and climate-relevant Amazon region. The detailed analysis of aerosol and CCN key properties and particularly the extracted CCN efficiency spectra with the associated fit parameters provide a basis for an in-depth analysis of aerosol-cloud interaction in the Amazon and beyond.
Yeast large ribosomal subunit (LSU) precursors are subject to substantial changes in protein composition during their maturation due to coordinated transient interactions with a large number of ribosome biogenesis factors and due to the assembly of ribosomal proteins. These compositional changes go along with stepwise processing of LSU rRNA precursors and with specific rRNA folding events, as revealed by recent cryo-electron microscopy analyses of late nuclear and cytoplasmic LSU precursors. Here we aimed to analyze changes in the spatial rRNA surrounding of selected ribosomal proteins during yeast LSU maturation. For this we combined a recently developed tethered tertiary structure probing approach with both targeted and high throughput readout strategies. Several structural features of late LSU precursors were faithfully detected by this procedure. In addition, the obtained data let us suggest that early rRNA precursor processing events are accompanied by a global transition from a flexible to a spatially restricted rRNA conformation. For intermediate LSU precursors a number of structural hallmarks could be addressed which include the fold of the internal transcribed spacer between 5.8S rRNA and 25S rRNA, the orientation of the central protuberance and the spatial organization of the interface between LSU rRNA domains I and III.
Este artigo tem como objetivo principal analisar a relação entre utopia negativa e catástrofe na Estética de Adorno. O filósofo argumenta que a arte moderna é associada a um tipo de utopia que não é uma representação positiva do que a sociedade deveria ser. A utopia negativa apenas mostra o que a sociedade não deveria ser. A obra de arte está então carregada de contradições de uma sociedade não reconciliada. Tal explica por que a arte moderna e nova é tão recorrentemente caracterizada pelo feio, o repulsivo, o negro e o catastrófico. Na formulação de Adorno, a obra de arte se constitui como negação determinada da sociedade administrada. Como tal, a obra de arte é também negação determinada da cultura administrada, isto é, sua constituição é dada pela negação determinada dos padrões da Indústria Cultural e da tradição artística.
Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T-cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and LFA-1 can generate intracellular signals, the immune cell adaptor protein linker for the activation of T cells (LAT) couples the TCR to downstream events. Here, we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on receptor clustering. Although increased affinity mediates adhesion, LFA-1 cross-linking induced the association and activation of the protein-tyrosine kinases FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the binding to adaptor complex GRB-2-SKAP1. LAT-GRB2-SKAP1 complexes were distinct from canonical LAT-GADs-SLP-76 complexes. LFA-1 cross-linking increased the presence of LAT-GRB2-SKAP1 complexes relative to LAT-GADs-SLP-76 complexes. LFA-1-FAK1 decreased T-cell-dendritic cell (DC) dwell times dependent on LAT-Y171, leading to reduced DO11.10 T cell binding to DCs and proliferation to OVA peptide. Overall, our findings outline a new model for LFA-1 in which the integrin can mediate both adhesion and de-adhesion events dependent on receptor cross-linking.
The important role of fire in regulating vegetation community composition and contributions to emissions of greenhouse gases and aerosols make it a critical component of dynamic global vegetation models and Earth system models. Over 2 decades of development, a wide variety of model structures and mechanisms have been designed and incorporated into global fire models, which have been linked to different vegetation models. However, there has not yet been a systematic examination of how these different strategies contribute to model performance. Here we describe the structure of the first phase of the Fire Model Intercomparison Project (FireMIP), which for the first time seeks to systematically compare a number of models. By combining a standardized set of input data and model experiments with a rigorous comparison of model outputs to each other and to observations, we will improve the understanding of what drives vegetation fire, how it can best be simulated, and what new or improved observational data could allow better constraints on model behavior. In this paper, we introduce the fire models used in the first phase of FireMIP, the simulation protocols applied, and the benchmarking system used to evaluate the models. We have also created supplementary tables that describe, in thorough mathematical detail, the structure of each model.
Purpose: Prisoners are at a particularly high risk of suicide. In contrast to other psychosocial risk factors it remains unclear to what degree the risk of suicide differs between prisoners with local citizenship and foreigners. In order to provide more detailed information for suicide prevention in prisons, this study aims to compare suicide rates (SR) between these populations in German criminal custody.
Methods: Based on a German national database of completed suicide in custody, suicides by prisoners were analysed and compared with epidemiological data of the prison population and the general population, stratified for German and foreign citizenship. Data analysis was adjusted for differences in the age distribution of both populations by calculating standard mortality ratios (SMR) for suicide.
Results: SR were higher in prisoners with German citizenship than those with foreign citizenship (SR = 76.5 vs. SR = 42.8, P<0.01). This association was not specific to the prison population, as the higher SR in citizens compared to non-citizens (SR = 19.3 vs. SR = 9.0, P<0.01) were also found in the general population. The association between prison suicide and citizenship was comparable in juvenile and adult prisoners, indicating its relevance to both the juvenile and adult detention systems.
Conclusion: Imprisonment is associated with a substantially increased risk of suicide in both German and non-German citizens, a finding which needs to be taken into consideration by the justice system. The lower suicide risk in non-German citizens is independent of whether or not they are in custody.
The dentate gyrus (DG) is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ). We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX) and a marker for mature neurons, calbindin (CB). Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs) during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL), indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains.
Neurogenesis of hippocampal granule cells (GCs) persists throughout mammalian life and is important for learning and memory. How newborn GCs differentiate and mature into an existing circuit during this time period is not yet fully understood. We established a method to visualize postnatally generated GCs in organotypic entorhino-hippocampal slice cultures (OTCs) using retroviral (RV) GFP-labeling and performed time-lapse imaging to study their morphological development in vitro. Using anterograde tracing we could, furthermore, demonstrate that the postnatally generated GCs in OTCs, similar to adult born GCs, grow into an existing entorhino-dentate circuitry. RV-labeled GCs were identified and individual cells were followed for up to four weeks post injection. Postnatally born GCs exhibited highly dynamic structural changes, including dendritic growth spurts but also retraction of dendrites and phases of dendritic stabilization. In contrast, older, presumably prenatally born GCs labeled with an adeno-associated virus (AAV), were far less dynamic. We propose that the high degree of structural flexibility seen in our preparations is necessary for the integration of newborn granule cells into an already existing neuronal circuit of the dentate gyrus in which they have to compete for entorhinal input with cells generated and integrated earlier.
Aufgrund soziokultureller Unterschiede im Bereich der Rechtsordnungen und demnach auch in den Terminologien kommen beim juristischen Übersetzen etliche Divergenzen zum Vorschein. Im Falle der Null- oder partiellen Äquivalenz zwischen den Termini der Ausgangs- und Zielsprache (AS und ZS) drohen nicht nur Missverständnisse zwischen den Parteien, sondern auch fatale Folgen. Um dem vorzubeugen, muss der Übersetzer als Kenner der Rechtsbegriffe und ihrer Rolle in den Rechtssystemen als Mediator nicht nur interlinguale, sondern v.a. interkulturelle Konflikte in Bezug auf das (Miss)Verstehen lösen. Die theoretischen Ansätze werden durch Erfahrungen aus einer weitläufigen Enquete unter sowohl Auftraggebern als auch unter beeidigten Übersetzern ergänzt
O Objetivo deste artigo consiste em apresentar fundamentos da proposta epistemológica de Jürgen Habermas, identificados em obras precedentes à sua Teoria do agir comunicativo. A partir de Teoria analítica da ciência e dialética será explorada a proposta do autor, tendo percorrido antecipadamente pela querela entre Popper e Adorno; posteriormente busca-se analisar como Habermas, em debate com seus contemporâneos, retrata sua proposta em Técnica e ciência como ideologia, considerado um marco para a Escola de Frankfurt.
There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases.
Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior. Here we investigated the relationship between callous-unemotional traits and gray matter volume using voxel-based morphometry in a large sample of typically-developing boys and girls (N = 189). Whole-brain multiple regression analyses controlling for site, total intracranial volume, and age were conducted in the whole sample and in boys and girls individually. Results revealed that sex and callous-unemotional traits interacted to predict gray matter volume when considering the whole sample. This interaction was driven by a significant positive correlation between callous-unemotional traits and bilateral anterior insula volume in boys, but not girls. Insula gray matter volume explained 19% of the variance in callous-unemotional traits for boys. Our results demonstrate that callous-unemotional traits are related to variations in brain structure beyond psychiatric samples. This association was observed for boys only, underlining the importance of considering sex as a factor in future research designs. Future longitudinal studies should determine whether these findings hold over childhood and adolescence, and whether the neuroanatomical correlates of callous-unemotional traits are predictive of future psychiatric vulnerability.
Mobulinae rays are part of Cabo Verde native biodiversity and belong to two extant genera, Manta and Mobula (Paig-Tran et al. 2013, Ward-Paige et al. 2013). Mobula spp. can be distinguished from Manta spp. by the mouth position, the shape of the cephalic fins and body size (Stevens 2011). Despite their large size, little is known about their population trends and precise distribution. They are particularly difficult to study in the wild and have restricted distributions (Ward-Paige et al. 2013, Croll et al. 2015).
Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase
(2017)
The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH–PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.
Früh- und Spätwerk eines Autors sind manchmal gegensätzlich. Hätte Fontane nur Geschwisterliebe und Mathilde Möhring hinterlassen, käme niemand auf die Idee, beides stamme aus derselben Feder. Auch die Beliebtheit verteilt sich oft unterschiedlich auf Werkteile, die zu unterschiedlicher Zeit entstanden sind. Der Fall Clemens Brentano ist allerdings speziell. Seine vor 1817 geschriebenen Werke haben ein anderes Publikum als die, die er nach 1817 schrieb. Zwei Leserschaften hat der Autor, beide ansehnlich, die des religiösen Spätwerks noch um ein Vielfaches größer als die des Romantik-OEuvres. Und zwischen den beiden Gruppen: keine Berührung. Die einen kennen nichts von dem, was die anderen verehren, und umgekehrt.
Wie kommt das? Was ist 1817 mit Clemens Brentano passiert? Welche Veränderungen zeigen um diese Zeit die Lebensumstände, das Schreiben, die Welt- und Selbstreflexion des Autors?
Das vorweg: Brentano sorgte für die literaturhistorisch beispiellose Werkscheidung selbst, indem er seinen Nachlass zweiteilte. Die religiösen Manuskripte bekam der fromme Bruder Christian, die übrigen die freigeistige Schwester Bettine. Entsprechend sollten die Werkteile sehr unterschiedliche Editionsverfahren durchlaufen. Schon am Wendepunkt sandte Brentano zudem das Signal, er werde in Zukunft anders schreiben als bisher. Nach dem Eindruck des Publikums, von Wolfgang Bunzel zusammengefasst, "gibt er 1817 seinen bisherigen Lebensinhalt, das Dichten, auf [...]. Fortan entstehen scheinbar nurmehr religiöse Erbauungsschriften."
Molecular detection of Bartonella henselae in 11 Ixodes ricinus ticks extracted from a single cat
(2017)
Background: Bartonella henselae is a highly prevalent, vector-borne pathogen. Transmission to humans and animals by ticks is discussed controversially. Here, we present a case report, where eleven Ixodes ricinus ticks all harbouring B. henselae DNA were removed from one single cat.
Results: The first feeding tick was tested positive for B. henselae DNA. The cat was also found to be seropositive for anti-B. henselae IgG antibodies (titer 1:640). Bartonella henselae was not cultivatable from cat blood. Ten more feeding ticks removed 7 months later contained also B. henselae DNA. Sequence analysis of the 16SrDNA and the 16S-23S internal transcribed spacer (ITS) region revealed 100% sequence homology between all ticks. Bartonella adhesin A (badA) and VirB/VirD4 type IV secretion system (virB) DNA were also detected in all ticks.
Conclusions: Our results indicate that cats may serve as a reservoir for adult ticks to acquire B. henselae. Whether this observation implies an increased threat for human and animal health needs to be resolved.
Willkommen
(2017)
We discuss the possibility to build a neutron target for nuclear reaction studies in inverse kinematics utilizing a storage ring and radioactive ion beams. The proposed neutron target is a specially designed spallation target surrounded by a large moderator of heavy water (D2O). We present the resulting neutron spectra and their properties as a target. We discuss possible realizations at different experimental facilities.
There is a curious gap in the scholarship on texts for young people: while series fiction has been an important stream of publishing for children and adolescents at least since the last decades of the nineteenth century, the scholarship on these texts has not been central to the development of theories on and criticism of texts for young people. The focus of scholarship is much more likely to be on stand-alone, high-quality texts of literary fiction. Kenneth Grahame’s The Wind in the Willows (1908), for example, has occupied critics in the field far more often and more significantly than all of the 46 popular novels about schoolgirls with similar plots that were published by Grahame’s contemporary, Angela Brazil (beginning in 1904 with A Terrible Tomboy). Literary fiction such as Grahame’s tends to be defined in terms of its singularity – the unique voice of the narrator, unusual resolutions to narrative dilemmas, intricate formal designs, and complicated themes – often specifically as distinct from the formulaic patterns of series fiction. Yet, curiously, scholars typically use examples from literary fiction to illustrate the common characteristics of books directed to young readers: it was Grahame’s book, and not Brazil’s books, that appeared in the Children’s Literature Association’s list Touchstones as one of the "distinguished children’s books" the study of which "will allow us to better understand children’s literature in general," according to Perry Nodelman, who chaired the committee that produced the list. (Nodelman 1985, p. 2) ...
Der Erzählforscher Johannes Merkel hat unlängst (2015) einen bemerkenswerten Überblick zur Gesamttradition des mündlichen Erzählens vorgelegt. Die folgenden Überlegungen, von einer Teilbesprechung dieser Neuerscheinung ausgehend, zielen grundsätzlich auf eine kritische Überprüfung von verschiedenen in der bisherigen Forschung für selbstverständlich gehaltenen Basisfaktoren (insbesondere den theoretischen Ansätzen von Nilsson und Parry). Dabei geht es zunächst einmal um jene allgemein vorausgesetzte vorgriechische Phase von oral poetry, auf die sich auch Merkel im 3. Kapitel unter dem Titel ‚Das singende Gedächtnis: Epenvortrag in Mittelasien und auf dem Balkan‘ bezog (105-148). Die neuere Forschung tendiert bekanntlich dazu, es habe eine längere oral poetry in den sog. "dunklen Jahrhunderten" zwischen 1200 und 850 v. Chr. noch vor Ausbildung der frühgriechischen Kultur gegeben; so z.B. der englische Althistoriker Robin Lane Fox (2008/11): "Ilias und Odyssee sind im Wesentlichen Werke der Mündlichkeit, die letzten in einem langen 'Zeitalter der Mündlichkeit'…". Eng damit verbunden waren Martin P. Nilssons Hypothese "The Mycenaen Origin of Greek Mythology" (1932) und der von Milman Parry seit 1928 konstituierte, von seinem Schüler Arthur B. Lord weiter entwickelte Ansatz, dass für frühgriechische Epen eine Vergleichbarkeit mit neueren Phasen mündlicher Epik z.B. auf dem Balkan gegeben sei. Merkels jüngste Ausführungen verstärken meine früheren Bedenken gegen dieses Gesamtkonzept.
Spätestens seit die SPD Martin Schulz zu ihrem Kanzlerkandidaten erkoren hat, stehen die Zeichen in der Politik auf Wahlkampf. In weniger als sechs Monate ist es so weit, die Parteienlandschaft ist nervös. Kaum äußert sich in diesen Tagen eine Partei zu einem Thema, wird dies als "Symbolpolitik" oder "Wahlkampfrhetorik" abgekanzelt. ...
The hallmark of classical Hodgkin lymphoma (cHL) is the presence of giant, mostly multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Whereas it has recently been shown that giant HRS cells evolve from small Hodgkin cells by incomplete cytokinesis and re-fusion of tethered sister cells, it remains unsolved why this phenomenon particularly takes place in this lymphoma and what the differences between these cell types of variable sizes are. The aim of the present study was to characterize microdissected small and giant HRS cells by gene expression profiling and to assess differences of clonal growth behavior as well as susceptibility toward cytotoxic intervention between these different cell types to provide more insight into their distinct cellular potential. Applying stringent filter criteria, only two differentially expressed genes between small and giant HRS cells, SHFM1 and LDHB, were identified. With looser filter criteria, 13 genes were identified to be differentially overexpressed in small compared to giant HRS cells. These were mainly related to energy metabolism and protein synthesis, further suggesting that small Hodgkin cells resemble the proliferative compartment of cHL. SHFM1, which is known to be involved in the generation of giant cells, was downregulated in giant RS cells at the RNA level. However, reduced mRNA levels of SHFM1, LDHB and HSPA8 did not translate into decreased protein levels in giant HRS cells. In cell culture experiments it was observed that the fraction of small and big HRS cells was adjusted to the basic level several days after enrichment of these populations via cell sorting, indicating that small and big HRS cells can reconstitute the full spectrum of cells usually observed in the culture. However, assessment of clonal growth of HRS cells indicated a significantly reduced potential of big HRS cells to form single cell colonies. Taken together, our findings pinpoint to strong similarities but also some differences between small and big HRS cells.
Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus. Translation of these findings would benefit from evidence of efficacy in non-status epilepticus models and validation in another species. Here, we report that electrographic seizures and convulsive behavior are strongly reduced in adult mice pre-treated with Ant-134 in the pentylenetetrazol model. Pre-treatment with Ant-134 did not affect the severity of status epilepticus induced by perforant pathway stimulation in adult rats, a toxin-free model of acquired epilepsy. Nevertheless, Ant-134 post-treatment reduced the number of rats developing spontaneous seizures by 86% in the perforant pathway stimulation model and Ant-134 delayed epileptiform activity in a rat ex vivo hippocampal slice model. The potent anticonvulsant effects of Ant-134 in multiple models may encourage pre-clinical development of this approach to epilepsy therapy.
β-barrel proteins mediate nutrient uptake in bacteria and serve vital functions in cell signaling and adhesion. For the 14-strand outer membrane protein G of Escherichia coli, opening and closing is pH-dependent. Different roles of the extracellular loops in this process were proposed, and X-ray and solution NMR studies were divergent. Here, we report the structure of outer membrane protein G investigated in bilayers of E. coli lipid extracts by magic-angle-spinning NMR. In total, 1847 inter-residue 1H–1H and 13C–13C distance restraints, 256 torsion angles, but no hydrogen bond restraints are used to calculate the structure. The length of β-strands is found to vary beyond the membrane boundary, with strands 6–8 being the longest and the extracellular loops 3 and 4 well ordered. The site of barrel closure at strands 1 and 14 is more disordered than most remaining strands, with the flexibility decreasing toward loops 3 and 4. Loop 4 presents a well-defined helix.
Aim: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.
Results: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.
Innovation and conclusion: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.
O artigo apresenta brevemente as possíveis implicações da recusa da clonagem, do DGPI e da eugenia liberal para o formalismo da ética discursiva, pois tal recusa poderia sugerir a eleição de um modo de vida privilegiado, (uma vida humana baseada na “inteireza do patrimônio genético”). Apresentamos os elementos do formalismo ético de Habermas e os argumentos centrais de sua crítica às intervenções eugênicas. Sugerimos que a defesa habermasiana da manutenção da indisponibilidade do patrimônio genético (por seu papel na autocompreensão ética do humano como ser livre e autônomo) situa essa matéria da filosofia moral na tensão entre a ação comunicativa, no qual o debate deveria ter sede, e a ação instrumental, que ameaça monopolizar as decisões sobre o tema.
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model. Initially, we found that IL-12−/− mice developed less severe colitis but are highly susceptible to colon cancer. By contrast, p47phox−/− mice showed lower tumor scores and fewer high grade tumors than wild-type (WT) littermates. Treatment with toll-like receptor 9 ligand CpG2216 significantly enhanced colitis in p47phox−/− mice, whereas tumor growth was simultaneously reduced. In tumor tissue of p47phox−/− mice, the IL-23/IL-17 axis was crucially hampered. IL-23p19 protein expression in tumor tissue correlated with tumor stage. Reconstitution of WT mice with IL-23p19−/− bone marrow protected these mice from colon cancer, whereas transplantation of WT hematopoiesis into IL-23p19−/− mice increased the susceptibility to tumor growth. Our study strengthens the divergent role of IL-12 and IL-23 in colon cancer development. With the characterization of p47phox as a novel modulator of both cytokines our investigation introduces a promising new target for antitumor strategies.
This paper discusses the syntax of relative clauses in European Portuguese (EP) by focussing on the status of the relativizer que in restrictive and appositive relative clauses. We propose a unified account of que in terms of a D-element and discuss the syntactic implications of this assumption for an adequate analysis of relative clauses in EP. We assume that relative que has properties of demonstrative and interrogative determiners. In restrictive object and subject relative clauses, que occurs as a transitive determiner [DP que [NP e]], which selects for a nominal complement, whereas in prepositional and appositive relative clauses, [DP que] is an intransitive determiner parallel to an e-type pronoun. We discuss the position of restrictive relative clauses in the DP containing the modified noun, and propose that they are merged pre-nominally, in the same fashion as demonstratives.
Die Themen Flucht und Migration stehen im Fokus dieser Jahrbuchausgabe. Während Flucht den unfreiwilligen Austritt aus einer gesellschaftlichen Einheit bedeutet, verweist der Begriff Migration auf den Versuch, in ein gesellschaftliches Gefüge einzutreten. Ein zentraler Unterschied liegt somit in sich dichotom gegenüberstehenden Ausgliederungs- und Eingliederungshandlungen. Eine Gemeinsamkeit stellt jedoch die Prozesshaftigkeit dar, die in literarisch sowie bildästhetisch umgesetzten Narrativen, wie zum Beispiel in Form von Graphic Novels, aufgegriffen wird. Die beiden oft aufeinander bezogenen Narrative Flucht und Migration werden in diesem Beitrag getrennt betrachtet und bilden zugleich die beiden zentralen Kapitel des Textes: Zuerst stehen Graphic Novels im Mittelpunkt, die ausschließlich Fluchtnarrative inszenieren, um danach eine spezifische Perspektive auf Migrationsnarrative einnehmen zu können. Gemäß der multimedialen Form dieses Mediums, das dazu tendiert, Fotografie, Illustration (vgl. Hescher 2016, S. 78) sowie Filmtechniken zu verbinden, muss auch die Zugangsweise einen interdisziplinä- ren Ansatz verfolgen, der laut den HerausgeberInnen des Readers Theorien des Comics zu den Stärken der Comicforschung gehöre. (Vgl. Reichert/Eder/Klar 2011, S. 10) Die Comicforschung, insbesondere jener Teilbereich, der sich mit dokumentarisch-grafischen Formen beschäftigt, liefert die Grundlage für die folgenden Überlegungen und die Fragestellung dieses Beitrags: Welche unterschiedlichen ästhetischen Formen werden eingesetzt, um die Themen Flucht und Migration grafisch darzustellen? ...
During the transition from early-modern societies to the nation states of the 19th and 20th centuries, the formation of the territorial state performed an important function. The combining of dominions to form a geographical and political unit could occur through the annexation of the weaker territory by the stronger one, but it could also occur with the mutual agreement of the political decision-makers of both territories. In the case of a union, a distinction emerged very early on between a real union and a personal union (or union of crowns). While in a real union agreements under international law were equally binding for both partners, the personal union assumed a special status, in which the person of the ruler was the only connection between the two states. However, this strictly legal definition only applied to the political institutions. Below the state level, there were forms of transfer that could give a personal union a special, transnational character. Academic opinion remains divided on the extent to which these connections, which are referred to using the term "composite statehood", constitute a Europe-wide development.
This paper considers the trend towards megaregionalism (TTIP, TPP) that became prominent in the trade domain in the last years of the Obama administration. While megaregionalism has fallen by the wayside since Trump’s inauguration, the underlying rationale for such treaties will most likely reassert itself rather soon. So there are structural issues that need to be discussed from a standpoint of global justice. In all likelihood, megaregionalism is detrimental to global justice. TTIP in particular, or anything like it, might derail any possibility for a trade organization to aid the pursuit of justice at the global level, and any possibility that trade will be used to that end. From the standpoint of global justice one must hope that megaregionalism does not replace WTO multilateralism. The global-justice framework used here is the grounds-of-justice approach offered in the author’s 2012 On Global Justice.