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Sphingosine-1-phosphate (S1P) lyase irreversibly cleaves S1P, thereby catalysing the ultimate step of sphingolipid degradation. We show here that embryonic fibroblasts from S1P lyase-deficient mice (Sgpl1−/−-MEFs), in which S1P and sphingosine accumulate, have features of Niemann-Pick disease type C (NPC) cells. In the presence of serum, overall cholesterol content was elevated in Sgpl1−/−-MEFs, due to upregulation of the LDL receptor and enhanced cholesterol uptake. Despite this, activation of sterol regulatory element-binding protein-2 was increased in Sgpl1−/−-MEFs, indicating a local lack of cholesterol at the ER. Indeed, free cholesterol was retained in NPC1-containing vesicles, which is a hallmark of NPC. Furthermore, upregulation of amyloid precursor protein in Sgpl1−/−-MEFs was mimicked by an NPC1 inhibitor in Sgpl1+/+-MEFs and reduced by overexpression of NPC1. Lysosomal pH was not altered by S1P lyase deficiency, similar to NPC. Interestingly, lysosomal Ca2+ content and bafilomycin A1-induced [Ca2+]i increases were enhanced in Sgpl1−/−-MEFs, contrary to NPC. These results show that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis.
Background: Long non-coding RNAs (lncRNAs) represent a novel class of non-coding RNAs having a crucial role in many biological processes. The identification of long non-coding homologs among different species is essential to investigate such roles in model organisms as homologous genes tend to retain similar molecular and biological functions. Alignment–based metrics are able to effectively capture the conservation of transcribed coding sequences and then the homology of protein coding genes. However, unlike protein coding genes the poor sequence conservation of long non-coding genes makes the identification of their homologs a challenging task.
Results: In this study we compare alignment–based and alignment–free string similarity metrics and look at promoter regions as a possible source of conserved information. We show that promoter regions encode relevant information for the conservation of long non-coding genes across species and that such information is better captured by alignment–free metrics. We perform a genome wide test of this hypothesis in human, mouse, and zebrafish.
Conclusions: The obtained results persuaded us to postulate the new hypothesis that, unlike protein coding genes, long non-coding genes tend to preserve their regulatory machinery rather than their transcribed sequence. All datasets, scripts, and the prediction tools adopted in this study are available at https://github.com/bioinformatics-sannio/lncrna-homologs.
Background: Up to 80% of breast cancer patients suffer from Cancer Related Cognitive Impairments (CRCI). Exercise is suggested as a potential supportive care option to reduce cognitive decline in cancer patients. This study will investigate the effects of a high-intensity interval endurance training (HIIT) on CRCI in breast cancer patients. Potentially underlying immunological and neurobiological mechanisms, as well as effects on patients’ self-perceived cognitive functioning and common cancer related side-effects, will be explored.
Methods: A single-blinded randomized controlled trial will be carried out. The impact of HIIT on CRCI will be compared to that of a placebo-intervention (supervised myofascial release training). Both interventions will be conducted simultaneously with the patients’ first-line chemotherapy treatment typically lasting 12–18 weeks. Fifty-nine women with breast cancer will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients’ change in cognitive testing performances, from baseline until the end of the exercise-intervention. The cognitive test battery, recommended by the International Cancer and Cognition Task Force to assess CRCI, will be used as primary measure. This includes the Hopkins Verbal Learning Test (learning/verbal memory), the Controlled Oral Word Association Test (verbal fluency) and the Trail-Making-Test A/B (attention/set-switching). The following endpoints will be assessed as secondary measures: Go-/No-Go test performance (response inhibition), self-perceived cognitive functioning, serum levels of pro- and antiinflammatory markers (tumor necrosis factor alpha, Interleukin-6, Interleukin-1 alpha, Interleukin-1 beta, C-reactive protein, Interleukin-1 receptor antagonist and Interleukin-10), serum levels of neurotrophic and growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1 and vascular endothelial growth factor), as well as common cancer-related side effects (decrease in physical capacity, fatigue, anxiety and depression, sleep disturbances, quality of life and chemotherapy compliance).
Discussion: This study will provide data on the question whether HIIT is an effective supportive therapy that alleviates CRCI in breast cancer patients. Moreover, the present study will help shed light on the underlying mechanisms of potential CRCI improving effects of exercise in breast cancer patients.
Trial registration: DRKS.de, German Clinical Trials Register (DRKS), ID: DRKS00011390, Registered on 17 January 2018.
Cyclic adenosine 3′,5′monophosphate (cAMP) regulated element binding protein (CREB) is a transcription factor involved in many different signaling processes including memory storage and retrieval. The mouse hippocampal neuronal cell line HT22 is widely used as a model system for neuronal cell death and cellular signal pathway investigations. For the present work a variant of HT22 with a stably expressed CRE-luciferase (CRE-luc) reporter (HT22CRE) is introduced, characterized and used to investigate cAMP-dependent and independent CRE-dependent signal processes. Trehalose (Mykose or 1-α-Glucopyranosyl-1-α-glucopyranosid) is a naturally occurring disaccharide consisting of two α,α′,1,1-glycosidic connected glucose molecules in a wide range of organisms but usually not found in mammals. Trehalose has been shown to activate autophagy, a process which regulates the degradation and recycling of proteins and organelles. The exact processes how trehalose application works on mammalian neuronal cells is not yet understood. The present work shows that trehalose application dose-dependently elevates CRE-luc activity in HT22 cells and acts synergistically with cAMP-elevating agents. In this pathway cAMP-dependent protein kinase (PKA) appears to be the most important factor and the stress kinase p38 and protein tyrosine kinases (PTKs) act as modulators.
Metabolic critical temperatures define the range of ambient temperatures where endotherms are able to minimize energy allocation to thermogenesis. Examining the relationship between metabolic critical temperatures and basal metabolic rates (BMR) provides a unique opportunity to gain a better understanding of how animals respond to varying ambient climatic conditions, especially in times of ongoing and projected future climate change. We make use of this opportunity by testing the heat dissipation limit (HDL) theory, which hypothesizes that the maximum amount of heat a species can dissipate constrains its energetics. Specifically, we test the theory’s implicit prediction that BMR should be lower under higher metabolic critical temperatures. We analysed the relationship of BMR with upper and lower critical temperatures for a large dataset of 146 endotherm species using regression analyses, carefully accounting for phylogenetic relationships and body mass. We show that metabolic critical temperatures are negatively related with BMR in both birds and mammals. Our results confirm the predictions of the HDL theory, suggesting that metabolic critical temperatures and basal metabolic rates respond in concert to ambient climatic conditions. This implies that heat dissipation capacities of endotherms may be an important factor to take into account in assessments of species’ vulnerability to climate change.
Purpose: There are little or no published data comparing the outcomes of ILUVIEN® (0.19 mg fluocinolone acetonide [FAc]) and OZURDEX® (0.7 mg dexamethasone [DEX]) implants in patients with diabetic macular edema (DME), and this case sought to compare their outcomes.
Methods: This case was extracted from a monocentric audit involving a pool of 25 patients (33 eyes) with DME and treated with a single FAc implant between October 2013 and December 2016. This case, a 61-year-old male with a pseudophakic lens, is from a patient that had received 4 intravitreal injections of a DEX implant prior to FAc implant and then was monitored for 3 years until re-treatment with a second FAc implant. Parameters measured included visual acuity (VA), central retinal thickness (CRT), and intraocular pressure (IOP).
Results: After the DEX implants, CRT transiently improved. In March 2014, the decision was taken to administer an FAc implant, and this led to a reduction in CRT below 300 µm (from a baseline of 748 µm), and this was sustained for 30 months. VA remained above 65 Early Treatment Diabetic Retinopathy Study letters to month 36, after which time a second FAc implant (in April 2017) was administered due to recurrence of edema and CRT decreased to below 300 µm and VA improved to 70 letters. Side effects included elevated IOP, which was effectively managed with IOP-lowering drops.
Conclusion: A single injection of FAc implant led to sustained improvements in CRT and VA that lasted for between 30 and 36 months, which is in contrast to the DEX implant where re-treatment was generally required within 6–7 months. After 36 months, re-treatment with the FAc implant again led to improved VA and CRT, and responses that were similar to those achieved with the first FAc implant.
Für die internationale Diskussion gibt es zunächst das Problem der Wissenschaftssprachen. In Polen spricht man, soweit ich das verstehe, stets vom "Staat der Piasten", selbst frühere Herrschaftsbildungen werden "Staat" genannt. Diese Gewohnheit der polnischen Kolleginnen und Kollegen steht in auffälligem Kontrast nicht nur zu deutschsprachigen, sondern auch zu frankophonen und anglophonen Historikern. In Frankreich unterscheidet man État und état. Die Orthographie (kleines oder großes "é") markiert das Konzept. Nur État mit Majuskel E bedeutet Staat, mit "l'état Carolingien" sagt niemand "der karolingische Staat". ...
Aim: To evaluate the ability of PillCamColon2 to visualize colonic segments missed by incomplete optical colonoscopy (OC) and to assess the diagnostic yield.
Methods: This prospective multicentre study included 81 patients from nine centres who underwent second-generation colon capsule endoscopy (CCE) following incomplete OC performed by an experienced gastroenterologist (> 1000 colonoscopies). Patients with stenosis were excluded. According to patient preferences, CCE was performed the following day (protocol A) after staying on clear liquids and 0.75 L Moviprep in the morning or within 30 d after new split-dose Moviprep (protocol B). Boosts consisted of 0.75 L and 0.25 L Moviprep, and phospho-soda was given as a rescue if the capsule was not excreted after seven hours.
Results: Seventy-four patients were analysed (51% of them in group A; 49% in group B). Bowel cleansing was adequate in 67% of cases, and CCE could visualize colonic segments missed by incomplete colonoscopy in 90% of patients under protocol A and 97% of patients under protocol B (P = 0.35, n.s.). Significant polyps including adenocarcinoma were detected in 24% of cases. Detection rates for all polyps and significant polyps per patient were similar in both protocols. Polyps were found predominantly in the right colon (86%) in segments that were not reached by OC. Extracolonic findings - such as reflux esophagitis, suspected Barrett esophagus, upper GI-bleeding, gastric polyps, gastric erosions and angiectasia - were detected in eight patients. PillCamColon2 capsule was retained in the ileum of one patient (1.4%) without symptoms and removed during an uneventful resection for unknown Crohn’s disease that was diagnosed as the cause of anemia, which was the indication for colonoscopy. CCE was well tolerated. One patient suffered from self-limiting vomiting after consuming the phospho-soda.
Conclusion: Second-generation CCE using a low-volume preparation is useful after incomplete OC, and it allows for the detection of additional relevant findings, but cleansing efficiency could be improved.
Bebilderte Multiple-Choice- (MC) Fragen sind ein integraler Bestandteil von schriftlichen Prüfungen in der Anatomie. In bebilderten MC-Fragen bezieht sich die schriftliche Frage auf verschiedene Typen von Abbildungen wie Röntgenaufnahmen, Mikrofotografien von histologischen Schnitten oder Zeichnungen von anatomischen Strukturen. Da das Hereinnehmen von Abbildungen in MC-Fragen das Abschneiden der Items beeinflussen kann, verglichen wir die Charakteristika von anatomischen Items getestet mit bebilderten und nicht bebilderten MC-Fragen in sieben Anatomieklausuren und in zwei schriftlichen Teilen des Ersten Abschnitts der Ärztlichen Prüfung (M1).
In dieser Studie verglichen wir 25 bebilderte und 163 nicht bebilderte MC-Fragen aus Anatomieklausuren und 27 bebilderte und 130 nicht bebilderte MC-Fragen aus dem schriftlichen Teil des M1 mit einem nicht parametrischen Test für ungepaarte Stichproben. Als Ergebnis waren keine signifikanten Unterschiede im Schwierigkeits- und Trennschärfeniveau zwischen bebilderten und nicht bebilderten MC-Fragen vorhanden, dasselbe ergab sich in einer nach MC-Frageformaten stratifizierten Analyse.
Wir schließen daraus, dass das bebilderte Itemformat für sich die Itemschwierigkeit nicht zu beeinflussen scheint. Die aktuellen Ergebnisse stimmen mit früheren retrospektiven Studien überein, die keine signifikanten Unterschiede zwischen Test- und Itemcharakteristika zwischen bebilderten und nicht bebilderten MC-Fragen zeigten.
Illustrated Multiple-choice questions (iMCQs) form an integral part of written tests in anatomy. In iMCQs, the written question refers to various types of figures, e. g. X-ray images, micrographs of histological sections, or drawings of anatomical structures. Since the inclusion of images in MCQs might affect item performance we compared characteristics of anatomical items tested with iMCQs and non-iMCQs in seven tests of anatomy courses and in two written parts of the first section of the German Medical Licensing Examination (M1).
In summary, we compared 25 iMCQs and 163 non-iMCQs from anatomy courses, and 27 iMCQs and 130 non-iMCQs from the written part of the M1 using a nonparametric test for unpaired samples. As a result, there were no significant differences in difficulty and discrimination levels between iMCQs and non-iMCQs, the same applied to an analysis stratified for MCQ formats.
We conclude that the illustrated item format by itself does not seem to affect item difficulty. The present results are consistent with previous retrospective studies which showed no significant differences of test or item characteristics between iMCQs and non-iMCQs.
Einleitung: Um junge Medizinstudierende auf die stetig wachsenden Anforderungen eines Arztes klinisch, wissenschaftlich sowie psycho-sozial allumfassend und kompetent besser vorzubereiten, sollten Universitäten eine enge, persönliche Erfahrungs- und Wissensvermittlung ermöglichen. Strukturierte Mentorenprogramme als Lösungsmodell klinische Aufgabenfelder früher in die vorklinische Lehre einfließen zu lassen, um somit eine begleitete Priorisierung des breiten, theoretisch geprägten universitären Lehrstoffes zu erleichtern, stellen einen vielversprechenden Ansatzpunkt dar.
Hier berichten wir über die Erfahrungen und Ergebnisse des vorklinischen Mentorenprogrammes der Universität Bonn, welches zum Wintersemester 12/13 eingeführt wurde.
Projektbeschreibung: Das Programm zeichnet sich durch das Konzept des peer-to-peer-Teachings in den Semestern der Vorklinik im Rahmen eines humanmedizinischen Regelstudienganges aus. In regelmäßigen, freiwilligen Kurstreffen mit verschiedenen klinischen Fallbeispielen soll Studierenden die Möglichkeit geboten werden, erworbene Kenntnisse aus den curricularen Grundlagenfächern eigenständig anzuwenden, sowie einen Kontakt mit einem persönlichen Ansprechpartner für Ratschläge und Hilfestellung zu gewährleisten. Auf diese Weise wird ein ungezwungener Erfahrungsaustausch ermöglicht, der den Studierenden eine Motivations- und Lernhilfe bietet, insbesondere für die mündliche Physikumsprüfung sowie für weitere Prüfungen des Studiums.
Ergebnisse: Über die letzten drei Jahre konnte die Teilnehmerzahl und das Interesse am Programm stetig gesteigert werden. Die Auswertung der gesammelten Evaluationen bestätigt eine sehr gute Kommunikation zwischen Tutor und Studierenden (über 80%), sowie durchweg gute bis sehr gute Qualität und Nützlichkeit der fachlichen, als auch sonstigen Tipps der Mentoren. Eine abschließende Bewertung der Erwartungen an das Mentorenprogramm wurde insgesamt auf einer Schulnotenskala stets als gut bis sehr gut bewertet (Wintersemester: sehr gut 64.8±5.0%, gut 35.2±5.0%, Sommersemester: sehr gut 83.9±7.5%, gut 16.1±7.5%)
Zusammenfassung: Zusammenfassend hat sich gezeigt, dass sich das Mentorenprogramm positiv auf die Entwicklung, Ausbildung und Zufriedenheit der Studienanfänger in der Bonner Vorklinik auswirkt.
Introduction: To better prepare young medical students in a thorough and competent manner for the ever increasing clinical, scientific, as well as psychosocial requirements, universities should enable a close, personal transfer of experience and knowledge. Structured mentoring programs are a promising approach to incorporate clinical subjects earlier into the preclinical training. Such a mentoring program facilitates the prioritization of concepts from a broad, theory-heavy syllabus.
Here we report the experiences and results of the preclinical mentoring program of Bonn University, which was introduced in the winter semester of 2012/2013.
Project desciption: The program is characterized by the concept of peer-to-peer teaching during the preclinical semesters of medical school. Regular, voluntary course meetings with different clinical case examples provide students the opportunity to apply knowledge acquired from the basic science curricula; furthermore, a personal contact for advice and support is ensured. Thus, an informal exchange of experiences is made possible, which provides to the students motivational and learning aids, in particular for the oral examination at the end of the premedical semesters as well as for other examinations during medical school.
Results: Over the course of the preceding three years the number of participants and the interest in the program grew steadily. The analysis of collected evaluations confirms very good communication between mentors and students (>80%), as well as consistently good to very good quality and usefulness in terms of the mentors’ subject-specific and other advice. The overall final evaluation of the mentoring program was always good to very good (winter semester: very good 64.8±5.0%, good 35.2±5.0%, summer semester: very good 83.9±7.5%, good 16.1±7.5%)
Summary: In summary, it has been shown that the mentoring program had a positive impact on the development, education and satisfaction of students beginning their preclinical semesters at Bonn University.
The aim of this paper is to present the results of an empirical analysis of the use of non-alphabetic graphic signs (e.g. asterisks, slashes, plus signs etc.) in the context of repairs in Russian and German informal electronic communication. The data for the analysis were taken from the “Mobile Communication Database MoCoDa” (http://mocoda.spracheinteraktion.de/), which contains Russian and German private electronic communication via SMS, WhatsApp and other short message services, and the “Dortmunder Chat-Korpus” (http://www.chatkorpus.tu-dortmund.de/korpora.html). This paper describes the functions of various graphic resources in the context of repairs in both data collections and compares the occurrences of these functions in current Russian and German computer-mediated communication. It concludes that particular signs in both data sets share the same subset of functions, but they differ in terms of how frequently these resources occur in each form of communication.
Background: Since 2009, IPF patients across Europe are recruited into the eurIPFreg, providing epidemiological data and biomaterials for translational research.
Methods: The registry data are based on patient and physician baseline and follow-up questionnaires, comprising 1700 parameters. The mid- to long-term objectives of the registry are to provide clues for a better understanding of IPF phenotype sub-clusters, triggering factors and aggravating conditions, regional and environmental characteristics, and of disease behavior and management.
Results: This paper describes baseline data of 525 IPF subjects recruited from 11/2009 until 10/2016. IPF patients had a mean age of 68.1 years, and seeked medical advice due to insidious dyspnea (90.1%), fatigue (69.2%), and dry coughing (53.2%). A surgical lung biopsy was performed in 32% in 2009, but in only 8% of the cases in 2016, possibly due to increased numbers of cryobiopsy. At the time of inclusion in the eurIPFreg, FVC was 68.4% ± 22.6% of predicted value, DLco ranged at 42.1% ± 17.8% of predicted value (mean value ± SD). Signs of pulmonary hypertension were found in 16.8%. Steroids, immunosuppressants and N-Acetylcysteine declined since 2009, and were replaced by antifibrotics, under which patients showed improved survival (p = 0.001).
Conclusions: Our data provide important insights into baseline characteristics, diagnostic and management changes as well as outcome data in European IPF patients over time.
Trial registration: The eurIPFreg and eurIPFbank are listed in ClinicalTrials.gov(NCT02951416).
Background: Bidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single-cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single-cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single-cell technologies are not yet established, in the context of BPs.
Results: We performed integrative analyses of novel human single-cell RNA-seq (scRNA-seq) data with bulk ChIP-seq and other epigenetics data. scRNA-seq data revealed distinct transcription states of BPs that were previously not recognized. We find associations between these transcription states to distinct patterns in structural gene features, DNA accessibility, histone modification, DNA methylation and TF binding profiles.
Conclusions: Our results suggest that a complex interplay of all of these elements is required to achieve BP-specific transcriptional output in this specialized promoter configuration. Further, our study implies that novel statistical methods can be developed to deconvolute masked subpopulations of cells measured with different bulk epigenomic assays using scRNA-seq data.
This commentary is an introduction for students to the Society of Environmental Toxicology and Chemistry (SETAC) and its Student Advisory Council (SAC). As young academics face challenges while trying to develop their careers, SETAC and the SAC help facilitate student involvement in the various communities within the society that can help to develop the students’ careers within the environmental sciences [e.g. the German Language Branch (GLB)]. This piece would also like to emphasize and pay homage to the continual cooperation between the SAC and the ESEU, which provides a scientific platform to communicate internationally and beyond the borders of SETAC, as well as offer heartfelt congratulations from the SAC to the GLB for their "20 Years SETAC GLB" and deep gratitude for their strong advocacy and support of the SAC.
Background and Objectives: Valuation of life (VOL) represents a construct capturing individuals’ active attachment to their life. The majority of studies on VOL were conducted in North America and Europe where personal autonomy and independence are highly valued, leaving open the question about the relevance of this construct in interdependence-oriented cultures. Using a framework of cross-cultural and life-span theories, the present study compared levels and predictors of VOL between the young-old and old-old individuals from Germany and Japan.
Research Design and Methods: Two hundred fifty-seven Germans and 248 Japanese, matched by age, gender, education, and IADL, answered a 5-item VOL scale and shared information on sociodemographic, social, and health resources.
Results: Germans’ VOL levels were higher than in Japanese participants. Both culture- and age-moderated predictions of VOL: education was significant only in the young-old Japanese, and close social partners mattered in the old-old, not in the young-old. Health determined VOL irrespective of culture and age.
Discussion and Implications: The findings suggest that cultural values and aging processes should be considered to better understand how individuals value their life and to help older adults to feel that his/her life is meaningful and worth living.
Experimental evidence supports that cortical oscillations represent multiscale temporal modulations existent in natural stimuli, yet little is known about the processing of these multiple timescales at a neuronal level. Here, using extracellular recordings from the auditory cortex (AC) of awake bats (Carollia perspicillata), we show the existence of three neuronal types which represent different levels of the temporal structure of conspecific vocalizations, and therefore constitute direct evidence of multiscale temporal processing of naturalistic stimuli by neurons in the AC. These neuronal subpopulations synchronize differently to local-field potentials, particularly in theta- and high frequency bands, and are informative to a different degree in terms of their spike rate. Interestingly, we also observed that both low and high frequency cortical oscillations can be highly informative about the listened calls. Our results suggest that multiscale neuronal processing allows for the precise and non-redundant representation of natural vocalizations in the AC.
Purpose: When squamous cell carcinoma of the buccal mucosa (BSCC) extends surrounding anatomical sites such as gingiva, retromolar triangle, or hard palate, it might be challenging to ensure adequate tumor coverage by sole interstitial brachytherapy due to the complexity of catheter implantation. By combining interstitial catheters with an enoral placed, individually assembled “oral spacer plus embedded catheters” device (hybrid of intracavitary-interstitial brachytherapy), it should be easier to deliver the necessary tumoricidal dose to irregular-shaped tumor volumes (clinical target volume – CTV) with improved conformity. The purpose of this analysis was to compare the dose distribution created by the hybrid of intracavitary-interstitial brachytherapy (HBT) with the dose distribution of an interstitial catheter only-approach, based on the interstitial catheters used for HBT (ISBT-only) by evaluating respective treatment plans (HBT plan vs. ISBT-only plan) for the treatment of early stage BSCC.
Material and methods: A retrospective analysis was performed for patients with localized BSCC treated between April 2013 and October 2017. All patients received sole HBT without additional external beam radiation therapy or planned neck dissection. Dosimetric parameters taken into account for comparison between actual HBT and virtual ISBT-only were CTV D90, CTV V100, CTV V150, CTV V200, mandible D2cc, and mucosal surface D2cc.
Results: Dosimetrically, HBT showed a trend toward better CTV D90 compared to ISBT-only. In addition, HBT demonstrated statistically better CTV V100 coverage compared to ISBT-only. There was no statistically significant difference with respect to CTV V150, CTV V200, and mucosal surface D2cc, while a trend was seen in better mandible D0.1cc between HBT and ISBT-only.
Conclusions: The HBT approach appears to enable improved dose coverage of irregular-shaped enoral tumor volumes compared to ISBT-only for patients with early stage BSCC.
Cryo-EM structures of KdpFABC suggest a K+ transport mechanism via two inter-subunit half-channels
(2018)
P-type ATPases ubiquitously pump cations across biological membranes to maintain vital ion gradients. Among those, the chimeric K+ uptake system KdpFABC is unique. While ATP hydrolysis is accomplished by the P-type ATPase subunit KdpB, K+ has been assumed to be transported by the channel-like subunit KdpA. A first crystal structure uncovered its overall topology, suggesting such a spatial separation of energizing and transporting units. Here, we report two cryo-EM structures of the 157 kDa, asymmetric KdpFABC complex at 3.7 Å and 4.0 Å resolution in an E1 and an E2 state, respectively. Unexpectedly, the structures suggest a translocation pathway through two half-channels along KdpA and KdpB, uniting the alternating-access mechanism of actively pumping P-type ATPases with the high affinity and selectivity of K+ channels. This way, KdpFABC would function as a true chimeric complex, synergizing the best features of otherwise separately evolved transport mechanisms.
"Die Goethe-Universität ist eine weltoffene Werkstatt der Zukunft mitten in Europa. 1914 von BürgerInnen für BürgerInnen gegründet, hat sie seit 2008 als autonome Stiftungsuniversität an diese Tradition wieder angeknüpft. Ihrer wechselvollen Geschichte kritisch verpflichtet, ist sie geleitet von den Ideen der Europäischen Aufklärung, der Demokratie und der Rechtsstaatlichkeit und wendet sich gegen Rassismus, Nationalismus und Antisemitismus. Die Goethe-Universität ist ein Ort argumentativer Auseinandersetzung; Forschung und Lehre stehen in gesellschaftlicher Verantwortung."
Dieses Leitbild strahlt an einem Freitagabend im Januar 2018 zwei Stunden lang über einem voll besetzten, unruhigen Hörsaal. Der groß an die Wand projizierte Text richtet sich an das Publikum einer Veranstaltung der "Frankfurter Bürgeruniversität" mit dem Titel "Diskurskultur im Zwielicht – Wie viel Meinungsfreiheit verträgt die Uni?" Die Atmosphäre ist für eine öffentliche Abendveranstaltung ungewöhnlich angespannt: Menschen mit unterschiedlichen politischen Einstellungen sitzen dicht beieinander, ein paar Burschenschaftler mit Schärpe nehmen die Mitte des Saales ein, es gibt Gerüchte, die AfD habe zu der Veranstaltung mobilisiert. ...
Bislang existieren kaum (musik-)psychologische Studien, welche die gesundheitliche Situation von Berufssänger/innen adressieren. Mit N = 313 Teilnehmenden handelt es sich bei der hier vorgestellten Forschungsarbeit um eine der bislang größten Studien, in welcher gesundheitspsychologische Aspekte bei Profisänger/innen untersucht wurden. Es konnte gezeigt werden, dass die Sänger/innen trotz hoher beruflicher Belastungen in 16 von 27 Burnout-Kennwerten niedrigere Werte aufweisen als die Personen der repräsentativen Vergleichsstichprobe. Bei den elf anderen Burnout-Kennwerten zeigte sich kein statistisch signifikanter Unterschied zwischen den beiden Gruppen. Mit den in den Regressionsanalysen berücksichtigten Prädiktoren lassen sich bis zu 40 Prozent des Kriteriums Burnout erklären. Als aussagekräftigste Prädiktoren konnten die Variablen Erholungskompetenz, Optimismus und Pessimismus identifiziert werden. Perfektionismus als unter Musiker/innen häufig stark ausgeprägte Persönlichkeitseigenschaft trug wider Erwarten kaum zur Vorhersage der Burnout-Ausprägungen der Berufssänger/innen bei. Für präventive und rehabilitative Maßnahmen mit Profisänger/innen lässt sich aus den Befunden mit Blick auf eine (potenzielle) Burnout-Erkrankung die Empfehlung ableiten, sich eher auf die Ressourcen der Musiker/innen (Erholungskompetenz, Optimismus) zu konzentrieren und weniger auf deren scheinbare Defizite (Perfektionismus).
Lehre im Bewegungsfeld Kämpfen an den sportwissenschaftlichen Hochschuleinrichtungen in Deutschland
(2018)
Obwohl sich verschiedene Formen des Kämpfens in zahlreichen Lehrplänen der Bundesländer wiederfinden und ein entsprechender Qualifizierungsbedarf angehender Lehrkräfte gefordert wird, liegen bislang kaum Daten zur Lehre im Bewegungsfeld Kämpfen an sportwissenschaftlichen Hochschuleinrichtungen vor. Im Frühjahr 2017 wurden deutschlandweit Personen mit lehrender oder koordinierender Tätigkeit im Bewegungsfeld Kämpfen zu grundlegenden Daten ihrer Lehrveranstaltung (u. a. Zielgruppe, Umfang, Verbindlichkeit), zur didaktisch-methodischen Gestaltung (u. a. Ziele, Inhalte, Methoden, Prüfungen) sowie zu ihrem Beschäftigungsverhältnis befragt. An 14 von 60 Standorten konnte kein entsprechendes Lehrangebot identifiziert werden. Die erfassten 54 Lehrangebote (beschrieben von 48 Personen aus 31 Einrichtungen) sind bezüglich der organisatorischen Rahmenbedingungen relativ gut vergleichbar: Etwa 83 % umfassen zwei SWS und ca. 74 % sind Wahlpflichtveranstaltungen. Heterogenität herrscht u. a. hinsichtlich der Lernziele sowie der eingesetzten Lehr-Lernformen. Die Bestandserhebung bietet eine fachbezogene Diskussionsgrundlage für die Ausgestaltung von Theorie und Praxis des Bewegungsfelds Kämpfen.
NMR and chromatography methods combined with mass spectrometry are the most important analytical techniques employed for plant metabolomics screening. Metabolomic analysis integrated to transcriptome screening add an important extra dimension to the information flow from DNA to RNA to protein. The most useful NMR experiment in metabolomics analysis is the proton spectra due the high receptivity of 1H and important structural information, through proton–proton scalar coupling. Routinely, databases have been used in identification of primary metabolites, however, there is currently no comparable data for identification of secondary metabolites, mainly, due to signal overlap in normal 1H NMR spectra and natural variation of plant. Related to spectra overlap, alternatively, better resolution can be find using 1H pure shift and 2D NMR pulse sequence in complex samples due to spreading the resonances in a second dimension. Thus, in data brief we provide a catalogue of metabolites and expression levels of genes identified in soy leaves and roots under flooding stress.
The present study aims at analyzing the role of nativeness, the amount of input in L1 acquisition and the multilingual competence in the performance of Italian–German bilingual speakers. We compare novel data from the performance of adult L2 learners (L1: Italian; late L2: German) and that of heritage speakers (heritage language: Italian; majority language: German) to previous data from monolingual speakers of Italian. The comparison deals with the produced word order at the syntax-discourse interface in sentences containing New Information Subjects in answers to questions that prompt the identification of the clausal subject. Overall, adult L2 speakers and heritage speakers perform alike but crucially differently from Italian monolinguals. These data reveal that multilingual proficiency determines an increased variety in the adopted answering strategies; in particular, the German-like strategy is active in Italian. Nativeness alone is thus no guarantee for a homogeneous performance across groups, nor do we find similar patterns of performance in speakers who grew up as monolinguals. Data also show heritage speakers’ sensitivity to verb classes, with answering strategies varying in accordance with the verb argument structure. Participants’ productions reveal an interesting relation in sentences with transitive verbs between subject position (pre-/postverbal) and object form (lexical DP/clitic pronoun).
Formation and segregation of cell lineages forming the heart have been studied extensively but the underlying gene regulatory networks and epigenetic changes driving cell fate transitions during early cardiogenesis are still only partially understood. Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq). By leveraging on cell-to-cell transcriptome and chromatin accessibility heterogeneity, we identify different previously unknown cardiac subpopulations. Reconstruction of developmental trajectories reveal that multipotent Isl1+ CPC pass through an attractor state before separating into different developmental branches, whereas extended expression of Nkx2-5 commits CPC to an unidirectional cardiomyocyte fate. Furthermore, we show that CPC fate transitions are associated with distinct open chromatin states critically depending on Isl1 and Nkx2-5. Our data provide a model of transcriptional and epigenetic regulations during cardiac progenitor cell fate decisions at single-cell resolution.
GTP cyclohydrolase (GCH1) governs de novo synthesis of the enzyme cofactor, tetrahydrobiopterin (BH4), which is essential for biogenic amine production, bioactive lipid metabolism and redox coupling of nitric oxide synthases. Overproduction of BH4 via upregulation of GCH1 in sensory neurons is associated with nociceptive hypersensitivity in rodents, and neuron‐specific GCH1 deletion normalizes nociception. The translational relevance is revealed by protective polymorphisms of GCH1 in humans, which are associated with a reduced chronic pain. Because myeloid cells constitute a major non‐neuronal source of BH4 that may contribute to BH4‐dependent phenotypes, we studied here the contribution of myeloid‐derived BH4 to pain and itch in lysozyme M Cre‐mediated GCH1 knockout (LysM‐GCH1−/−) and overexpressing mice (LysM‐GCH1‐HA). Unexpectedly, knockout or overexpression in myeloid cells had no effect on nociceptive behaviour, but LysM‐driven GCH1 knockout reduced, and its overexpression increased the scratching response in Compound 48/80 and hydroxychloroquine‐evoked itch models, which involve histamine and non‐histamine dependent signalling pathways. Mechanistically, GCH1 overexpression increased BH4, nitric oxide and hydrogen peroxide, and these changes were associated with increased release of histamine and serotonin and degranulation of mast cells. LysM‐driven GCH1 knockout had opposite effects, and pharmacologic inhibition of GCH1 provided even stronger itch suppression. Inversely, intradermal BH4 provoked scratching behaviour in vivo and BH4 evoked an influx of calcium in sensory neurons. Together, these loss‐ and gain‐of‐function experiments suggest that itch in mice is contributed by BH4 release plus BH4‐driven mediator release from myeloid immune cells, which leads to activation of itch‐responsive sensory neurons.
Background: Effects of playing high stringed bow instruments on the upper body posture have not been analysed so far. The instrument-specific seating position when playing in an orchestra is compared to the habitual seating position.
Methods: Three dimensional back scans were performed in 13 professional violinists and viola players of a radio orchestra (8 f / 5 m). Trunk position in their habitual seating position and in the instrument- specific seating position imitating playing was compared. Statistical differences were calculated using Wilcoxon Matched Pairs Test with Bonferroni Holm correction.
Results: Significant differences were found between the seated position with instrument and without (p < 0.001, 0.03, 0.02 or 0.01) in the spine (trunk length, sagittal trunk decline, lumbar bending angle, maximal rotation, standard deviation rotation, lumbar lordosis), the shoulder (scapula distance, scapula rotation, scapula angle right) and pelvis distance.
Conclusions: Playing an instrument changes the static seating position by increased rotation of the spine and specific shoulder adaptations holding the instrument (left arm) and the bow (right arm), with minor effects on the pelvis. This forced position may result in chronic health effects. The method used in this study is an approach to better understand the involved muscular structures and possible resulting health damages.
Background/Aims: An estimated 80 million people worldwide are infected with viremic hepatitis C virus (HCV). Even after eradication of HCV with direct acting antivirals (DAAs), hepatic fibrosis remains a risk factor for hepatocarcinogenesis. Recently, we confirmed the applicability of microfibrillar-associated protein 4 (MFAP4) as a serum biomarker for the assessment of hepatic fibrosis. The aim of the present study was to assess the usefulness of MFAP4 as a biomarker of liver fibrosis after HCV eliminating therapy with DAAs.
Methods: MFAP4 was measured using an immunoassay in 50 hepatitis C patients at baseline (BL), the end-of-therapy (EoT), and the 12-week follow-up visit (FU). Changes in MFAP4 from BL to FU and their association with laboratory parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, the AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4), and albumin were analyzed.
Results: MFAP4 serum levels were representative of the severity of hepatic fibrosis at BL and correlated well with laboratory parameters, especially APRI (Spearman correlation, R²=0.80). Laboratory parameters decreased significantly from BL to EoT. MFAP4 serum levels were found to decrease from BL and EoT to FU with high statistical significance (Wilcoxon p<0.001 for both).
Conclusions: Our findings indicate that viral eradication resulted in reduced MFAP4 serum levels, presumably representing a decrease in hepatic fibrogenesis or fibrosis. Hence, MFAP4 may be a useful tool for risk assessment in hepatitis C patients with advanced fibrosis after eradication of the virus.
G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.
Die jährlich im Vorfeld der DGfS-Tagung veranstaltete Arbeitstagung Linguistische Pragmatik fand 2012 vor besonderem Hintergrund statt: Es war zugleich die erste Jahrestagung des neu gegründeten, seit 01.01.2012 bestehenden Vereins Arbeitskreis Linguistische Pragmatik. Zu diesem Anlass haben die Organisatoren (Constanze Spieß, Elke Diedrichsen und Jörg Bücker) ein Rahmenthema gewählt, das pragmatisch orientierte Linguistinnen und Linguisten der verschiedensten Forschungsrichtungen zusammenbringt: Sprachkritik und Sprachwandel. ...
Background: Previous experimental research on testosterone (T) and psychological traits is inconclusive. Thus, we performed the first large-scale observational study of the association between T and dispositional optimism / pessimism.
Methods: We used prospective data from 6,493 primary-care patients (3,840 women) of the DETECT study (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment), including repeated immunoassay-based measurement of serum T and optimism / pessimism assessed by the revised Life-Orientation Test (LOT-R). Cross-sectional and longitudinal associations of baseline T and one-year change in T with optimism and pessimism were investigated using age- and multivariable-adjusted regression models.
Results: Cross-sectional analyses showed no association of T with optimism or pessimism in both sexes. Longitudinal analyses also showed no association of baseline T with optimism or pessimism at four-year follow-up. Multivariable analyses of total LOT-R score yielded similarly non-significant results (β-coefficient per unit change in T for men: -0.01 (95% CI: -0.24–0.22), women: 0.08 (-0.03–0.20)). Furthermore, change in T was not related to optimism or pessimism at four-year follow-up.
Conclusions: The present observational study of a large-scale prospective sample showed no association of T with optimism or pessimism. Integrating further experimental and interventional evidence from alternative methodological approaches would strengthen this conclusion and establish stronger evidence about the potential hormonal basis of psychological traits.
The bluebottle blow fly Calliphora vicina is a common species distributed throughout Europe that can play an important role as forensic evidence in crime investigations. Developmental rates of C. vicina from distinct populations from Germany and England were compared under different temperature regimes to explore the use of growth data from different geographical regions for local case work. Wing morphometrics and molecular analysis between these populations were also studied as indicators for biological differences. One colony each of German and English C. vicina were cultured at the Institute of Legal Medicine in Frankfurt, Germany. Three different temperature regimes were applied, two constant (16°C & 25°C) and one variable (17–26°C, room temperature = RT). At seven time points (600, 850, 1200, 1450, 1800, 2050, and 2400 accumulated degree hours), larval lengths were measured; additionally, the durations of the post feeding stage and intrapuparial metamorphosis were recorded. For the morphometric and molecular study, 184 females and 133 males from each C. vicina population (Germany n = 3, England n = 4) were sampled. Right wings were measured based on 19 landmarks and analyzed using canonical variates analysis and discriminant function analysis. DNA was isolated from three legs per specimen (n = 61) using 5% chelex. A 784 bp long fragment of the mitochondrial cytochrome b gene was sequenced; sequences were aligned and phylogenetically analyzed. Similar larval growth rates of C. vicina were found from different geographic populations at different temperatures during the major part of development. Nevertheless, because minor differences were found a wider range of temperatures and sampling more time points should be analyzed to obtain more information relevant for forensic case work. Wing shape variation showed a difference between the German and English populations (P<0.0001). However, separation between the seven German and English populations at the smaller geographic scale remained ambiguous. Molecular phylogenetic analysis by maximum likelihood method could not unambiguously separate the different geographic populations at a national (Germany vs England) or local level.
Background: Incisional heia is a frequent complication of midline laparotomy. The use of mesh in hernia repair has been reported to lead to fewer recurrences compared to primary repair. However, in Ventral Hernia Working Group (VHWG) Grade 3 hernia patients, whose hernia is potentially contaminated, synthetic mesh is prone to infection. There is a strong preference for resorbable biological mesh in contaminated fields, since it is more able to resist infection, and because it is fully resorbed, the chance of a foreign body reaction is reduced. However, when not crosslinked, biological resorbable mesh products tend to degrade too quickly to facilitate native cellular ingrowth. Phasix™ Mesh is a biosynthetic mesh with both the biocompatibility and resorbability of a biological mesh and the mechanical strength of a synthetic mesh. This multi-center single-arm study aims to collect data on safety and performance of Phasix™ Mesh in Grade 3 hernia patients.
Methods: A total of 85 VHWG Grade 3 hernia patients will be treated with Phasix™ Mesh in 15 sites across Europe. The primary outcome is Surgical Site Occurrence (SSO) including hematoma, seroma, infection, dehiscence and fistula formation (requiring intervention) through 3 months. Secondary outcomes include recurrence, infection and quality of life related outcomes after 24 months. Follow-up visits will be at drain removal (if drains were not placed, then on discharge or staple removal instead) and in the 1st, 3rd, 6th, 12th, 18th and 24th month after surgery.
Conclusion: Based on evidence from this clinical study Depending on the results this clinical study will yield, Phasix™ Mesh may become a preferred treatment option in VHWG Grade 3 patients.
Trial registration: The trial was registered on March 25, 2016 on clinicaltrials.gov: NCT02720042.
Operating in a reverberating regime enables rapid tuning of network states to task requirements
(2018)
Neural circuits are able to perform computations under very diverse conditions and requirements. The required computations impose clear constraints on their fine-tuning: a rapid and maximally informative response to stimuli in general requires decorrelated baseline neural activity. Such network dynamics is known as asynchronous-irregular. In contrast, spatio-temporal integration of information requires maintenance and transfer of stimulus information over extended time periods. This can be realized at criticality, a phase transition where correlations, sensitivity and integration time diverge. Being able to flexibly switch, or even combine the above properties in a task-dependent manner would present a clear functional advantage. We propose that cortex operates in a "reverberating regime" because it is particularly favorable for ready adaptation of computational properties to context and task. This reverberating regime enables cortical networks to interpolate between the asynchronous-irregular and the critical state by small changes in effective synaptic strength or excitation-inhibition ratio. These changes directly adapt computational properties, including sensitivity, amplification, integration time and correlation length within the local network. We review recent converging evidence that cortex in vivo operates in the reverberating regime, and that various cortical areas have adapted their integration times to processing requirements. In addition, we propose that neuromodulation enables a fine-tuning of the network, so that local circuits can either decorrelate or integrate, and quench or maintain their input depending on task. We argue that this task-dependent tuning, which we call "dynamic adaptive computation," presents a central organization principle of cortical networks and discuss first experimental evidence.
Background: Tick-borne encephalitis (TBE) is endemic in southern and eastern districts of Germany. Approximately 10–14% of the infected individuals suffer from long-term disability and in 1.5–3.6% the course is fatal. Two well-tolerated vaccines are available, which provide high protection and which have been confirmed in several field studies. Here we investigate clinical course, long-term outcome and cerebrospinal fluid (CSF) characteristics of TBE cases with a prior history of any vaccination as well as real vaccination breakthrough (VBT).
Methods: A case series of 11 patients with a prior history of vaccination, part of a recently published lager cohort of 111 TBE cases. Evaluation included clinical data, degree of disability (modified RANKIN scale, mRS) and analysis of CSF and serum samples. Furthermore, metadata for extended analysis on clinical outcome of TBE with VBT were analysed.
Results: One patient had a clear VBT and ten of them had irregular vaccinations schedules (IVS). Infection severity did not differ in patients with IVS as compared to a non-vaccinated control cohort (median mRS: both 3.0) but these patients showed a stronger cellular immune response as measured by CSF pleocytosis (IVS, 205 cells/μL versus non-vaccinated control, 114 cell/μL, P < 0.05) and by differential pattern of CSF (intrathecal) immunoglobulin synthesis. However, shift analysis of VBT metadata using linear-by-linear association revealed a more serious course of TBE in patients with VBT than in a non-vaccinated control cohort (χ2 = 9.95, P = 0.002). Furthermore, ordinal logistic regression analysis showed that VBT patients had an age-corrected, 2.65 fold (CI: 1.110–6.328; χ2 = 4.813; p = 0.028) significant higher risk to suffer from moderate or severe infections, respectively.
Conclusion: A history of IVS surprisingly seems to have no impact on the clinical course of TBE but may leave marks in the specific brain immune response. VBT patients, however, carry an age-independent, significant risk to experience a severe infection.
The identification of pathological atrophy in MRI scans requires specialized training, which is scarce outside dedicated centers. We sought to investigate the clinical usefulness of computer-generated representations of local grey matter (GM) loss or increased volume of cerebral fluids (CSF) as normalized deviations (z-scores) from healthy aging to either aid human visual readings or directly detect pathological atrophy.
Two experienced neuroradiologists rated atrophy in 30 patients with Alzheimer's disease (AD), 30 patients with frontotemporal dementia (FTD), 30 with dementia due to Lewy-body disease (LBD) and 30 healthy controls (HC) on a three-point scale in 10 anatomical regions as reference gold standard. Seven raters, varying in their experience with MRI diagnostics rated all cases on the same scale once with and once without computer-generated volume deviation maps that were overlaid on anatomical slices. In addition, we investigated the predictive value of the computer generated deviation maps on their own for the detection of atrophy as identified by the gold standard raters.
Inter and intra-rater agreements of the two gold standard raters were substantial (Cohen's kappa κ > 0.62). The intra-rater agreement of the other raters ranged from fair (κ = 0.37) to substantial (κ = 0.72) and improved on average by 0.13 (0.57 < κ < 0.87) when volume deviation maps were displayed. The seven other raters showed good agreement with the gold standard in regions including the hippocampus but agreement was substantially lower in e.g. the parietal cortex and did not improve with the display of atrophy scores. Rating speed increased over the course of the study and irrespective of the presentation of voxel-wise deviations.
Automatically detected large deviations of local volume were consistently associated with gold standard atrophy reading as shown by an area under the receiver operator characteristic of up to 0.95 for the hippocampus region. When applying these test characteristics to prevalences typically found in a memory clinic, we observed a positive or negative predictive value close to or above 0.9 in the hippocampus for almost all of the expected cases. The volume deviation maps derived from CSF volume increase were generally better in detecting atrophy.
Our study demonstrates an agreement of visual ratings among non-experts not further increased by displaying, region-specific deviations of volume. The high predictive value of computer generated local deviations independent from human interaction and the consistent advantages of CSF-over GM-based estimations should be considered in the development of diagnostic tools and indicate clinical utility well beyond aiding visual assessments.
Mitochondrial complex I has a key role in cellular energy metabolism, generating a major portion of the proton motive force that drives aerobic ATP synthesis. The hydrophilic arm of the L-shaped ~1 MDa membrane protein complex transfers electrons from NADH to ubiquinone, providing the energy to drive proton pumping at distant sites in the membrane arm. The critical steps of energy conversion are associated with the redox chemistry of ubiquinone. We report the cryo-EM structure of complete mitochondrial complex I from the aerobic yeast Yarrowia lipolytica both in the deactive form and after capturing the enzyme during steady-state activity. The site of ubiquinone binding observed during turnover supports a two-state stabilization change mechanism for complex I.
RNA not only translates the genetic code into proteins, but also carries out important cellular functions. Understanding such functions requires knowledge of the structure and dynamics at atomic resolution. Almost half of the published RNA structures have been solved by nuclear magnetic resonance (NMR). However, as a result of severe resonance overlap and low proton density, high-resolution RNA structures are rarely obtained from nuclear Overhauser enhancement (NOE) data alone. Instead, additional semi-empirical restraints and labor-intensive techniques are required for structural averages, while there are only a few experimentally derived ensembles representing dynamics. Here we show that our exact NOE (eNOE) based structure determination protocol is able to define a 14-mer UUCG tetraloop structure at high resolution without other restraints. Additionally, we use eNOEs to calculate a two-state structure, which samples its conformational space. The protocol may open an avenue to obtain high-resolution structures of small RNA of unprecedented accuracy with moderate experimental efforts.
Loss-of-function mutations of progranulin are associated with frontotemporal dementia in humans, and its deficiency in mice is a model for this disease but with normal life expectancy and mild cognitive decline on aging. The present study shows that aging progranulin deficient mice develop progressive polydipsia and polyuria under standard housing conditions starting at middle age (6-9 months). They showed high water licking behavior and doubling of the normal daily drinking volume, associated with increased daily urine output and a decrease of urine osmolality, all maintained during water restriction. Creatinine clearance, urine urea, urine albumin and glucose were normal. Hence, there were no signs of osmotic diuresis or overt renal disease, other than a concentrating defect. In line, the kidney morphology and histology revealed a 50% increase of the kidney weight, kidney enlargement, mild infiltrations of the medulla with pro-inflammatory cells, widening of tubules but no overt signs of a glomerular or tubular pathology. Plasma vasopressin levels were on average about 3-fold higher than normal levels, suggesting that the water loss resulted from unresponsiveness of the collecting tubules towards vasopressin, and indeed aquaporin-2 immunofluorescence in collecting tubules was diminished, whereas renal and hypothalamic vasopressin were increased, the latter in spite of substantial astrogliosis in the hypothalamus. The data suggest that progranulin deficiency causes nephrogenic diabetes insipidus in mice during aging. Possibly, polydipsia in affected patients - eventually interpreted as psychogenic polydipsia - may point to a similar concentrating defect.
Full reconstruction of large lobula plate tangential cells in Drosophila from a 3D EM dataset
(2018)
With the advent of neurogenetic methods, the neural basis of behavior is presently being analyzed in more and more detail. This is particularly true for visually driven behavior of Drosophila melanogaster where cell-specific driver lines exist that, depending on the combination with appropriate effector genes, allow for targeted recording, silencing and optogenetic stimulation of individual cell-types. Together with detailed connectomic data of large parts of the fly optic lobe, this has recently led to much progress in our understanding of the neural circuits underlying local motion detection. However, how such local information is combined by optic flow sensitive large-field neurons is still incompletely understood. Here, we aim to fill this gap by a dense reconstruction of lobula plate tangential cells of the fly lobula plate. These neurons collect input from many hundreds of local motion-sensing T4/T5 neurons and connect them to descending neurons or central brain areas. We confirm all basic features of HS and VS cells as published previously from light microscopy. In addition, we identified the dorsal and the ventral centrifugal horizontal, dCH and vCH cell, as well as three VSlike cells, including their distinct dendritic and axonal projection area.
A wealth of data has elucidated the mechanisms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neurotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhibition in distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinhibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition.
Neuro-ophthalmological signs and symptoms are common in the emergency department but are a frequent source of diagnostic uncertainties. However, neuro-ophthalmological signs often allow a precise neuro-topographical localization of the clinical problem. A practical concept is presented how to perform a neuro-ophthalmological examination at the bedside and to interpret key findings under the aspect of emergency medicine with limited resources.
In this paper pronominalization is analyzed in reference to the fictional creatures in the literary work of Guillermo del Toro’ in order to study whether the choice of pronoun serves the function of expressing attitudes towards fictional creatures, such as zombies and vampires, in a way that makes the contexts and the characters’ subjective perceptions the dominant factors and consequently puts aside the semantic or grammatical status of the referent. The paper also investigates whether inanimate pronouns (it/its, which), are used in association with detached appraisal, callousness and dehumanization, and whether personal pronouns (he/his, she/her, and who/whom) are used with attachment, closeness and humanization. These two categories of pronouns (personal and inanimate) are normally distinct, i.e., in most contexts they cannot be used interchangeably. The study of the characteristics of fictional creature pronominalization can shed light on how we use pronouns in order to create creatures that exist only in our imagination, and how a variety of different attitudes towards them is expressed through this specific linguistic tool. In relation to del Toro’s zombies and vampires, it can be argued that the pronominalization serves a certain purpose in order to dehumanize them, differentiate the dead vampire/zombies from the living humans, and to point out the before and the after of the transition between life and death. The pronominalization in reference to fairies, although complicated and not completely consistent, shows a clear tendency towards a correlation between animal–like creatures and inanimate pronouns. In regards to del Toro’s trolls, the pronominalization follows a more consistent pattern, which clearly serves the function of expressing different kinds of attitudes towards the creatures such as detached appraisal and dehumanization, on the one hand, and friendship and alliance, on the other.
In this article, we profile an empirically grounded, cognitive approach to immersion in digital fiction by combining text-driven stylistic analysis with insights from theories of cognition and reader-response research. We offer a new analytical method for immersive features in digital fiction by developing deictic shift theory for the affordances of digital media. We also provide empirically substantiated insights to show how immersion is experienced cognitively by using Andy Campbell and Judi Alston’s (2015) digital fiction piece WALLPAPER as a case study. We add ‘interactional deixis’ and ‘audible deixis’ to Stockwell’s (2002) model to account for the multimodal nature of immersion in digital fiction. We also show how extra-textual features can contribute to immersion and thus propose that they should be accounted for when analysing immersion across media. We conclude that the analytical framework and reader response protocol that we develop here can be adapted for application to texts across media.
This paper discusses aspects of direct speech in James Joyce’s story "The Sisters". The story is often analyzed with special attention to the gaps and ellipses in the utterances, which are usually read as omissions, evasions, or uncomfortable silences, and thus as indicative of some transgressive behaviour of the dead priest who is at the centre of the dialogues. In this article we explore the hypothesis that the utterances in question show features that are quite common in natural spoken language and thus may also be read as literary techniques to create authentic oral discourse. This hypothesis is not intended to invalidate previous interpretations, but to introduce an additional aspect of interpretation that has been neglected so far. In the context of a literary work, features of natural spoken language acquire new meaning, and the very attempt to narrow the gap between literary and natural spoken language appears as inauthentic, ominous and as an artistic strategy to express the unspeakable. The story thus evokes suspicion and a feeling of eeriness while also offering narrative and linguistic information that allows for a more empathic assessment of the characters. We use quantitative methods of analysis and linguistic data from corpora of (authentic) spoken language to substantiate our hypothesis. As "The Sisters" is a rather short story and the present study is, in several respects, exploratory, our claims and hypotheses need to be confirmed and validated by more exhaustive research into Joyce’s major works.
In order to achieve the goals of social commentary and moral judgement pursued in her novels, Jane Austen describes and evaluates different aspects of her characters’ personalities: social attitude, intellectual qualities and moral traits (Lodge 1966). Mansfield Park (1814) is one of her novels in which this moral awareness is most acute. In order to construct a community of shared values with her readers, Austen skilfully alternates different points of view as sources of evaluation. We propose an analysis of the first chapter of Mansfield Park that addresses this dialogic dimension by focusing on the resources of engagement, the subsystem of Appraisal Theory with which speakers/writers express their commitment to the truth of a proposition and their willingness to open the negotiation space to other voices (Martin & White 2005: 97).
The linguistic subtlety and complexity of Jane Austen’s writing is a challenge to translators, who must try to identify all the concurrent interpretation possibilities and reproduce them in the target language. In this article we compare the English source text with various translations into Spanish, Catalan and German. Our analysis focuses on the lexicogrammatical realisations of engagement such as verba dicendi, epistemic expressions, lexical choices with a distinct attitudinal load, and also on the development of narration – as far as that is possible in a study centering on the first chapter –, since it is often the case that narrator stance is modified as the text unfolds.
We discuss fragments of narrator discourse, direct speech and indirect/free indirect speech and consider the advantages of the framework to uncover changes in the evaluative dimension of meaning that affect the readings the translations will afford in their target society, from character building to the articulation of points of view.
The present study investigates the representation of non-standardised varieties of English in literary prose texts. This is achieved by creating and annotating a corpus of literary texts from Scotland, West Africa, and Southeast Asia. The analysis addresses two major topics. Firstly, the extent of representation reveals clearly distinct feature profiles across regions, coupled with varying feature densities. Feature profiles are also relevant to individual characters, as certain traits such as social status, ethnicity, or age can be signalled by linguistic means. The second topic, accuracy of representation, compares the features observed in literary texts with descriptions of the actual varieties, and suggests that representations of varieties may differ from their real-life models in the sense that highly frequent features may be absent from texts, while less frequent but more emblematic ones, or even invented ones, may be used by authors to render a variety of English in their texts.
It has been noted (Perkins, 2009; Zwaan, 1999; Zwaan & Radvansky, 1998) that causality, character, location, and time are the four main aspects of narrative discourse, even if not attended to by listeners or readers in equal ways. For example, character is highly ranked, and the locational/spatial components have often been underestimated for English narratives (see Perkins, 2009, for a review). Relative to the ranking, there is no inherent reason why character needs to be highly ranked, and locational/spatial information is in fact important in English narrative discourse (Perkins, 2009). I instead suggest that there are linguistic and cultural factors in the ranking of these aspects of discourse. Specifically, I suggest that causality is (probably) the highest ranked component, in languages that have a ranking, with the other three elements being linked to causality more or less strongly, depending on linguistic and cultural factors; it is possible that some languages do not rank narrative elements or that some elements are ranked as highly as others. In English, the strongest link is between causality and character. However, this is not universal.
In a survey of fifty-eight languages from thirty language families, including an in-depth study of Hobongan, an Austronesian language spoken by approximately two thousand people on the island of Borneo that I am in the process of describing, it is found that there is a great deal of cross-linguistic variation, to the extent that it is possible that each logically possible combination of narrative elements is present in the world’s languages.
Abrupt switches between different tenses (past-to-present, present-to-past) are known from oral narratives and medieval literature in Romance languages, but there is little consensus about their function and interpretation. In this study, we combine corpus-linguistic tools with experimental methods and quantitative analysis to shed light on the use of tense switches in a medieval Icelandic prose text (Hrafnkels saga freysgoða). Specifically, we part-of-speech tagged all words in Hrafnkels saga freysgoða and then determined where verbs exhibit tense switches. In a second step, we had 19 subjects mark all parts in the saga they consider climactic so as to study the overall as well as subject-specific correlations between climaxness and tense switches. In the vast majority of subjects, we observe the expected correlation, and for most of these it is significant. We discuss the findings with regard to their implications for tense switching as a performative device and the position of sagas on an orality-literacy continuum.
Smith (1968) argues that poems may end with formal changes which produce an experience of closure in the reader. I argue that formal changes do not directly cause an experience of closure. Instead, changes in poetic form always demand increased processing effort from the reader, whether they involve new forms, shifts from more to less regular form, or from less to more regular form. I use relevance theory (Sperber and Wilson 1995) to argue that the increased processing effort encourages the reader to formulate rich and relevant thoughts, including the thought "this poem has closure". Closure is thus the content of a thought rather than a type of experience. I further argue that "closure" is a term whose meaning cannot be fully understood, which makes the thought "this poem has closure" into a schematic belief of the kind which Sperber shows has great richness and productivity. This is one of the reasons that the thought "this poem has closure" achieves sufficient relevance to justify the effort put into processing the end of the poem.
The article addresses the question of who reports the dialogue in fictional texts featuring an unreliable narrator. Since no human being can remember and reproduce lengthy conversations accurately, some narrative theorists attribute direct speech representation to the author instead of the character narrator. This means that the speech of other characters may be reported reliably even if the narrator is totally unreliable. The narrator’s version of the events may then be contradicted by others, which allows the reader to perceive his biases. However, Kazuo Ishiguro’s An Artist of the Floating World illustrates the fact that direct speech reports, too, can be distorted by the narrator’s subjectivity, especially his emotions. In Ishiguro’s novel, the narrator’s grief and depression lead him to misremember and invent past conversations. Following Meir Sternberg, the article argues that the reliability of speech reporting in unreliable narration must be determined on a case-by-case basis. The text must signal that the narrator’s speech reporting is unreliable. In the absence of a signal, the reader is supposed to disregard any deviations from verbatim reproduction and to accept the transgression of the limits of human memory.
This article approaches literary translation from a contact-linguistic perspective and views translation as a language contact situation in which the translator "moves" between the source and target language. The study touches upon the possible linguistic effects of the source text on the translated text and relates the translation-mediated cross-linguistic influence to other language-contact situations. The study investigates the use of Finnish passive in a corpus of literary texts consisting of Finnish translations from Estonian and German and comparable non-translated Finnish literary texts. The translated texts are compared with non-translated ones by using corpus-linguistic tools, and the results are related to a previous contact-linguistic study on the use of the Finnish passive in spoken interviews of Finnish migrants in Estonia. The main objective is to test methodological tools that could be used for this kind of comparative purposes.
In addition, the study approaches the question whether translation as a type of language contact affects the use of the Finnish passive in a similar way as an oral language contact situation. All in all, the study shows that there are some features that differentiate the investigated literary translations from non-translated Finnish texts but the evidence is not unambiguous. The article discusses the possible reasons for the mainly non-conclusive results of the analysis and points out factors that should be taken into account in future studies, such as the size of the sub-corpora and the possibly biased text or genre specific stylistic characteristics. The methodology clearly has to be adjusted and more in-depth methods developed in order to acquire a fuller picture of the Finnish passive in literary texts and to confirm what is author, translator, genre or source-language specific in the use of the Finnish passive.
This article analyzes the representation of linguistic variation in the Finnish translations of four Swedish coming-of-age stories depicting migrant or minority perspectives: Mikael Niemi’s 2000 Popular Music from Vittula, Jonas Hassen Khemiri’s 2003 Ett öga rött, Marjaneh Bakhtiari’s 2005 Kalla det vad fan du vill, and Susanna Alakoski’s 2006 Svinalängorna. Through an analysis of speech and thought representation techniques and focalization, the article explores the role played by literature and translation in the materialization of dialects and sociolects as bounded entities. The paper argues that linguistic and social hybridity, on which the reception of minority and migrant literatures often focuses, is accompanied by the reification of new varieties conceived as authentic expressions of migrant and minority experience. Literature and translation are active agents in such processes, which are largely based on cultural, discursive, and cognitive constraints that condition the interpretation of each text.
C’est trop auch! the translation of contemporary French literature featuring urban youth slang
(2016)
The French post-colonial novel has recently been witnessing the emergence of urban youth language or français contemporain des cités (Goudaillier 2001). This linguistic variety allows underprivileged youths from multi-ethnic suburbs to rebel against authority by deliberately violating standard language norms. Its characteristics include frequent lexical input from immigrant languages, in particular Arabic and English, and the use of verlan at the morphological level, with the latter involving a form of back slang using syllabic inversion, which can be recurrently applied to heighten its coding function. In view of the social rejection of this ‘antilanguage’ (Halliday 1978), it has had difficulty penetrating into literature. However, this is now beginning to change, with urban youth discourse appearing in a number of novels, mostly by young ‘post-migration’ writers (Geiser 2008), such as Faïza Guène, Insa Sané and Rachid Djaïdani. While this language variety has mainly been dealt with by sociolinguists, some of the novels concerned are now crossing borders, and a multi-disciplinary approach to this phenomenon is now called for, combining linguistic, literary and translatological tools.
The transfer of this heterolingual genre does indeed raise a number of issues. For example, if we assume that translation is a cultural-political practice (Venuti 2008), what options do translators have to convey the resistant discourse of young immigrant slang users? How will the relationship between language use and social identity manifest itself in the target text? And how can a contrastive linguistic analysis of the features of urban youth language help to resolve translation problems? I will draw on a corpus of French and Dutch novels as well as some translations from French in an attempt to answer these questions.
Several translation scholars have recognised translation as a form of discourse mediation or discourse presentation (see, for example, Mossop 1998). In line with this, "universals" of translation have also been re-framed in the larger context of discourse mediation, as mediation universals rather than something strictly translationspecific (Ulrych 2009). In the present article, this line of enquiry is developed by comparing some of the alleged universals of translation, namely standardization and explicitation, with insights from literary and narratological studies on the nature of discourse presentation. The notion of reportive or interpretative interference (Sternberg 1982) and Fludernik’s (1993) claim that all represented discourse is typical and schematic in nature seem to bear curious resemblance to the notion of standardization or normalization, posited as a possible universal of translation (Mauranen & Kujamäki 2004). Drawing on the results of my earlier research (Kuusi 2011), I present examples of free indirect discourse (FID) used in Dostoevsky’s novel Crime and Punishment with their translations into Finnish. Analyzing the translations, I demonstrate how in
translations, the narratological and literary-theoretical notions of reportive interference and typification/schematization coincide with the translation-theoretical notions of explicitation and standardization.
The article deals with Finnish translations of varieties of spoken language in fiction from the late 19th century to the beginning of the 2000s. It presents the central findings of a comprehensive study on the changes and developments of translational norms in Finnish literature. The study is based on a corpus consisting of 200 literary works (the original and its translations are counted as one work), representing various genres: literary fiction, young-adult fiction, as well as genre fiction (romance and crime). During this 100-year period, the use of colloquial variants in translations has strongly increased, influenced by the changing literary and linguistic norms of original Finnish literature. The norms of different literary genres, however, vary, and rich, non-standard variation can be found in translated works from different periods.
This article is a linguistic study of David Bellos’ indirect translation of Ismail Kadare’s The File on H (1997), a novel first published in 1980-1981 in the Albanian literary review Nëntori, and translated into English on the basis of Jusuf Vrioni’s French version, Le Dossier H (1989). Also called "double", "mediated" or "second-hand", indirect translation is an understudied phenomenon, often criticised by scholars because of its greater distance to the original. Cay Dollerup (2000: 23), for example, argues that the grammatical structure of the mediating language (ML) obscures the distinctions made in the source language (SL), and that possible "mistakes" in the ML may be repeated in the target language (TL). Do fidelity and loyalty to the author become weakened in Bellos’ indirect translation? To what extent is such weakening discernible linguistically? And does this particular case of indirect translation reveal notable patterns or recurring types of linguistic shifts between ST and TT? Showing that some of the features specific to Kadare’s Albanian writing are tempered in the doubly-translated English text, yet highlighting that similar shifts occur in the three language directions involved, this article demonstrates that changes between ST and TT may occur in indirect translation regardless of the strategies adopted by MT – thus challenging the hypothesis that linguistic shifts in indirect translation follow a single or consistent pattern.
Thomas Mann’s Der Tod in Venedig (1912) owes much of its fame in English to a translation from 1928 by Helen Tracy Lowe-Porter. The novella however has in fact been translated many times – first by Burke (1924, with a revised edition following in 1970), and, after Lowe-Porter, by Luke (1988), Koelb (1994), Appelbaum (1995), Neugroschel (1998), Chase (1999), Heim (2004), Doege (2007) and Hansen & Hansen (2012). Most of these versions are neither known to readers nor discussed in academic literature. This paper, which comes as part of a larger study on linguistic creativity in Der Tod in Venedig, focuses on the use of neologisms by Mann and what happens to them in (re)translation. Relying on a digital corpus composed of the complete set of English retranslations and a corpus-based methodology, the paper argues that, despite the extended time period between the publications and different translation conditions, neologisms are treated uniformly by the translators. Mann’s coinages are nearly always obliterated through normalisation and, if preserved, demonstrate less creativity overall than in the ST, raising questions about the Retranslation Hypothesis (RH) which proposes that early TT versions tend to domesticate while later ones increasingly foreignise.
This special issue of the International Journal of Literary Linguistics offers seven state-of-the-art contributions on the current linguistic study of literary translation. Although the articles are based on similar data – literary source texts and their translations – they focus on diverse aspects of literary translation, study a range of linguistic phenomena and utilize different methodologies. In other words, it is an important goal of this special issue to illuminate the current diversity of possible approaches in the linguistic study of translated literary texts within the discipline of translation studies. At the same time, new theoretical and empirical insights are opened to the study of the linguistic phenomena chosen by the authors of the articles and their representation or use in literary texts and translations. The analyzed features range from neologisms to the category of passive and from spoken language features to the representation of speech and multilingualism in writing. Therefore, the articles in this issue are not only relevant for the study of literary translation or translation theory in general, but also for the disciplines of linguistics and literary studies – or most importantly, for the cross-disciplinary co-operation between these three fields of study.
The common theme that all these articles share is how the translation process shapes, transfers and changes the linguistic properties of literary texts as compared to their sources texts, other translations or non-translated literary texts in the same language and how this question can be approached in research. All articles provide new information about the forces that direct and affect translators’ textual choices and the previously formulated hypotheses about the functioning of such forces. The articles illustrate how translators may perform differently from authors and how translators’ and authors’ norms may diverge at different times and in different cultures. The question of how translation affects the linguistic properties of literary translations is approached from the viewpoint of previously proposed claims or hypotheses about translation. In the following, we will introduce these viewpoints for readers who are not familiar with the recent developments in translation studies. At the same time, we will shortly present the articles in this issue.
This article analyzes the dynamics of fictional dialogue in three short stories by the Finnish author Rosa Liksom. These stories are constructed almost entirely of dialogue, with minimal involvement on the part of the narrator. We adopt two different approaches to dialogue. First, we analyze dialogue from a micro level, as interaction between the characters within the storyworlds, then from a more holistic perspective, paying attention to how dialogue contributes to the rhetorical structure and ethical interpretation of the stories. We show that resorting mainly to dialogue as a narrative mode works as a way of depicting tensions between Liksom’s characters, and between them and the surrounding fictional world. This, in turn, engages the reader in an interpretative process to understand the story’s logic both within the fictional worlds and on the level of communication between the implied author and the authorial audience.
This article explores the uses and functions of dialogue in Frank McCourt’s memoir Angela’s Ashes. Taking conversational dialogue and fictional dialogue as points of comparison, the article argues that dialogue in autobiographical writing is essentially constructed, albeit not in the same way as fictional dialogue is. Dialogue as a means of dramatisation raises questions regarding factuality and fictionality. In McCourt’s memoir, dialogue is shown to serve numerous functions: characterisation and stereotyping; selfpositioning and indirect stance-marking; the creation of verisimilitude, humour and reader involvement.
This special issue is devoted to a cross-disciplinary investigation of a specific literary phenomenon, fictional dialogue. Fictional dialogue is used to refer to passages of character-character conversation within a literary text. More specifically, the articles of the issue deal with fictional dialogue as a narrative mode in prose fiction. The issue aims to engender an appreciation and a better understanding of the workings of dialogue by drawing on the insights and methods from both literary studies and linguistics. These methods include a rhetorical-ethical approach to narrative, cognitive and “natural” narratology, the study of everyday conversational storytelling, and Conversation Analysis (CA). Combining these methods helps us to understand that while dialogue is a central means to depict character-character relationships it also serves other levels of communication in a narrative and thus contributes to the reader's comprehension of the narrative design's rhetorical and ethical dimensions. The articles also suggest that while understanding dialogue depends partly on the reader’s experiences of real-life conversation, the interpretation of dialogue is determined by the overall design of a literary text and the historically changing conventions.
Metaphors we may not live by
(2016)
Metaphors We Live By created an immediate stir in 1980, and it continues to spur interest in cognitive linguistics, cognitive stylistics, and metaphor theory. This article uses both collocations and random samples of words used in conceptual metaphors to search for corpus evidence of the pervasiveness of conceptual metaphor that was unavailable to Lakoff and Johnson. Some metaphors, such as TIME IS MONEY, are pervasive in giant natural language corpora. Others, such as MORE IS UP, are frequent in clearly and consciously metaphorical forms, but relatively rare in the basic forms that would clearly show that we use metaphor to understand more abstract concepts in terms of concrete ones. Some, including ARGUMENT IS WAR, that Lakoff and Johnson discuss throughout their book, are poorly represented. Some gaps in evidence probably result from multiple ways of expressing a complex conceptual metaphors, but others suggest that intuitive plausibility is an insecure basis for argument.
Most of us receive numerous spam e-mails, texts that in one or the other way try to convince us to engage in the transaction of enormous sums of money, promising enormous benefits. In reality, such scam e-mails are fraudulent attempts to swindle money from unsuspecting Internet users. Language, its social contexts, and the composition of texts play a crucial role in the scammers’ strategies to approach their victims. This article uncovers and discusses some of the linguistic strategies by which scammers try to shape a sense of identity and mutual relationship – in the face of virtual anonymity –, and to involve their readers personally. In their attempts to get the recipients involved, scammers combine cultural indexicals, interactional roles, and narrative strategies. The analysis distinguishes three different narrative strategies in scam e-mails: Based on first, second, and third person stories, scammers establish links with the recipients by combining fictional content with real-world contexts. Some of the narratives display quite elaborate and artful traits and involve prototypical functions of traditional fairy tales. Hereby they implicitly connect the story content with the interactional roles of e-mail communication.
Establishing coherent identity patterns for literary characters in novels is a difficult task. In this respect, we assume that readers rely on pre-stored cultural models in order to construct mental models of the text content, including character identity. By significantly extending the approach by Van Dijk and Kintsch and going beyond the related accounts of Schneider and of Culpeper, we aim to clarify the constitutive role of conceptual metaphor as proposed by Lakoff et al. in processes of literary identity construction. The analysis of a corpus of three contemporary novels supports our claim that conceptual metaphors and the mapping of domains involved interact with cultural models and connect text phenomena to such prior knowledge structures. On this basis, we provide an integrated model of literary identity construction which acknowledges the constitutive value of conceptual metaphors in literary identity construction.
Frederick Turner and Ernst Pöppel (1983) proposed that lines of metrical poetry tend to measure three seconds or less when performed aloud, and that the metrical line is fitted to a three second "auditory present" in the brain. In this paper I show that there are faults both in their original argument, and in the claims which underlie it. I present new data, based on the measurement of line durations in publicly available recorded performances of 54 metrical poems; in this corpus, lines of performed metrical verse are often longer than three seconds: 59% of the 1155 lines are longer than 3 seconds, 40% longer than 3.5 seconds and 26% longer than 4 seconds. On the basis of weaknesses in the original paper, and the new data presented here, I propose, against Turner and Pöppel, that there is no evidence that lines of verse are constrained by a time-limited psychological capacity.
Editorial
(2013)
The aim of this two-part special issue of The International Journal of Literary Linguistics is to probe the implications of the cognitive turn in literary linguistics that has gone hand in hand with the field’s growing appreciation of pragmatics at the end of the twentieth century (as illustrated e.g. by MacMahon, Mey, Verdonk and Weber). The view, increasingly shared by literary linguists, that literature is a communicative endeavour between text (author) and reader has resulted in a heightened interest in the cognitive abilities that ultimately make this communication possible. Yet the ease with which the buzzword ‘cognition’ sometimes is applied to explain these abilities and processes (which are often only assumed to exist rather than substantiated with empirical evidence) seems to be at odds not least with the fact that the cognitive sciences are far from a uniform field yielding fixed and finite results. Indeed, whether or not all language phenomena are underpinned by innate cognitive rules is an issue that remains a bone of contention amongst scholars, as does the nature of these cognitive rules themselves. Even a cognitive grammarian like Ronald Langacker warns against jumping to premature conclusions about the natural foundations of language (14) and avoids making such claims in his own work. ...
Invasive treatment of NSTEMI patients in German chest pain units – evidence for a treatment paradox
(2018)
Background: Patients with non ST-segment elevation myocardial infarction (NSTEMI) represent the largest fraction of patients with acute coronary syndrome in German Chest Pain units. Recent evidence on early vs. selective percutaneous coronary intervention (PCI) is ambiguous with respect to effects on mortality, myocardial infarction (MI) and recurrent angina. With the present study we sought to investigate the prognostic impact of PCI and its timing in German Chest Pain Unit (CPU) NSTEMI patients.
Methods and results: Data from 1549 patients whose leading diagnosis was NSTEMI were retrieved from the German CPU registry for the interval between 3/2010 and 3/2014. Follow-up was available at median of 167 days after discharge. The patients were grouped into a higher (Group A) and lower risk group (Group B) according to GRACE score and additional criteria on admission. Group A had higher Killip classes, higher BNP levels, reduced EF and significant more triple vessel disease (p < 0.001). Surprisingly, patients in group A less frequently received early diagnostic catheterization and PCI. While conservative management did not affect prognosis in Group B, higher-risk CPU-NSTEMI patients without PCI had a significantly worse survival.
Conclusions: The present results reveal a substantial treatment gap in higher-risk NSTEMI patients in German Chest Pain Units. This treatment paradox may worsen prognosis in patients who could derive the largest benefit from early revascularization.
The following mission statements by linguists and literary scholars working in different institutional and cultural contexts and at different stages of their careers are intended to map out the terrain covered by this journal. They tell similar stories about how these scholars came to cross the disciplinary boundary that too often divides their two fields, and they reveal a number of shared interests and emphases. But they also highlight the diversity of methodologies to which this journal is open – from metrics and stylistics to the cognitive sciences and Systemic Functional Grammar. The hopes and expectations voiced by the authors are partly pragmatic, expressing the wish that the journal’s Open Access format will have a broader reach than a journal published in the "traditional" way would, notably to colleagues outside of Western Europe. They also, however, emphasise the journal’s potential to shape our conception of "literary linguistics" and, therefore, to make an innovative contribution to shaping what continues to be a contested and often misunderstood "field".
The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
Background: This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis.
Methods: This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity.
Results: 1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ≥ 20% (baseline to day 1) or ≥ 50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0–45.9) and 43.1 (10.1–184.0)).
Conclusions: MR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.
Neurons collect their inputs from other neurons by sending out arborized dendritic structures. However, the relationship between the shape of dendrites and the precise organization of synaptic inputs in the neural tissue remains unclear. Inputs could be distributed in tight clusters, entirely randomly or else in a regular grid-like manner. Here, we analyze dendritic branching structures using a regularity index R, based on average nearest neighbor distances between branch and termination points, characterizing their spatial distribution. We find that the distributions of these points depend strongly on cell types, indicating possible fundamental differences in synaptic input organization. Moreover, R is independent of cell size and we find that it is only weakly correlated with other branching statistics, suggesting that it might reflect features of dendritic morphology that are not captured by commonly studied branching statistics. We then use morphological models based on optimal wiring principles to study the relation between input distributions and dendritic branching structures. Using our models, we find that branch point distributions correlate more closely with the input distributions while termination points in dendrites are generally spread out more randomly with a close to uniform distribution. We validate these model predictions with connectome data. Finally, we find that in spatial input distributions with increasing regularity, characteristic scaling relationships between branching features are altered significantly. In summary, we conclude that local statistics of input distributions and dendrite morphology depend on each other leading to potentially cell type specific branching features.
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.
Gemeinsam mit dem Fach Germanistik an der Universität Stockholm richten die Fächer Germanistik und Translation Deutsch der Universität Helsinki in Zusammenarbeit mit dem Goethe-Institut Finnland und der Botschaft der Republik Österreich in Finnland vom 23. bis 25. August 2017 die siebente internationale Tagung zur kontrastiven Medienlinguistik aus. Der thematische Rahmen dieser Tagung lautet: Medienkulturen - Multimodalität und Intermedialität.
Die Jubiläumstagung feierte das 25jährige Bestehen des Franz Werfel-Programms. Viele Tagungsbeiträge analysierten Werke und Tendenzen der Literatur der österreichischen Moderne, andere suchten Erotik bei vergessenen oder jüngeren Autoren.
Die regelmäßig stattfindende internationale Konferenz des Franz-Werfel-Programms vertieft die Zusammenarbeit der Wissenschaftlerinnen und Wissenschaftler und bietet einen spannenden Perspektivenaustausch nicht nur im Rahmen der Auslandsgermanistik, sondern auch zwischen ihr und der Literaturwissenschaft in Österreich.
Vom 16. bis 18. März 2017 fand am Institut für Germanistik der Universität Wroclaw eine internationale sprachwissenschaftliche Konferenz statt. Die Tagung mit dem Rahmenthema 'Intra- und interlinguale Zugänge zur deutschen Phraseologie und Parömiologie' wurde vom Lehrstuhl für Angewandte Linguistik des Instituts für Germanistik der Universität Wroclaw in Zusammenarbeit mit dem Institut für Slawistik (FR Westslawistik) der Universität Leipzig veranstaltet.
In diesem Beitrag wird gezeigt, dass das Wort Volk seit einigen Jahren ein Schlüsselwort politischer Diskurse in Deutschland darstellt. Dies bedeutet im Sinne Wolf-Andreas LIEBERTs (2003) nicht nur, dass es von unterschiedlichen gesellschaftlichen Akteuren verwendet wird, um gegensätzliche Ideale und Antworten auf die Frage nach der eigenen individuellen und kollektiven Identität zu formulieren, sondern auch selbst zum Gegenstand von Kontroversen und damit diskursbestimmend wird. Dass diese jüngere Entwicklung eine besondere ist, machen Analysen deutlich, die die Verwendung des Wortes in unterschiedlichen und hinsichtlich nationaler und sozialer Identitäten dynamischen Phasen der deutschen Geschichte in den Blick nehmen.
Dort, wo es zu einem intensiven kulturellen Kontakt, Austausch und Transfer zwischen Gemeinschaften kommt, lassen sich Kategorien wie Identität und Alterität nicht immer scharf voneinander trennen, sondern erscheinen eher als "ständig zu aktualisierende soziale Konstruktionen" (NEULAND 2013: 168). Sie können zudem auch zu transkulturellen innovativen sprachlichen Schöpfungen führen. Die Sprache ist wegen ihrer identitätskonstitutiven Funktion fester Bestandteil des Modells der multiplen Sprachidentität von Marijana KRESIĆ (2007). Ausgehend von diesem Modell wird im Beitrag das enge Verhältnis von Identitätskonstruktion - Standardsprache - Sprachgebrauch diskutiert und anhand von ausgewählten Beispielen dargestellt. Die identitätskonstitutive Funktion der Sprache basiert auf der Selektion von Normen aus dem Sprachsystem, wobei der Sprechende durch die Verwendung sprachlicher Zeichen, "seine (soziale und/oder personale Identität) [begründet], d.h. er markiert, wer er als Individuum ist bzw. welcher sozialen Gruppe er zugehört" (KRESIĆ 2007: 19). Im Rahmen der Besprechung dieses Konzepts wird geprüft, wie Formen interkulturellen Sprachgebrauchs (z. B. Kiezdeutsch) in dieses Modell eingefügt werden können.
In diesem Beitrag wurden deutsche Entlehnungen in der albanischen Mundart in Kosova untersucht, welche in verschiedenen semantischen Bereichen verwendet werden. Schriftliche Quellen zu diesen Germanismen fehlen völlig, daher wurden sie durch mündliche Befragung von Informanten inventarisiert. Den Schwerpunkt dieser Untersuchung bilden der Bekanntheitsgrad und die Akzeptanz dieser Lehnwörter. Die Befragung hat ergeben, dass die Lehnwörter in den hier untersuchten semantischen Bereichen durchschnittlich von über 70% der Befragten erkannt wurden. Im Allgemeinen konnten keine großen Unterschiede im Erkennungsgrad bei männlichen und weiblichen Befragten festgestellt werden, wohingegen bei der Variable Alter eine etwas größere Diskrepanz beobachtet wurde, was das Erkennen oder Nichterkennen der deutschen Entlehnungen anging.
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
In diesem Beitrag wird korpusbasiert, qualitativ und aus kontrastiver Sicht anhand ausgewählter Einzelbeispiele untersucht, welchen Beitrag die Frame-Semantik bei der Analyse konzeptueller Metaphern im aktuellen Migrationsdiskurs in der deutschen und italienischen Presse leisten kann. Sie macht es möglich, unterschiedliche Perspektivierungen bei der Betrachtung des Phänomens herauszukristallisieren, da semantische Frames ein facettenreiches Angebot für den Blickwinkel der Betrachtung bereitstellen. Auch Metaphern selbst besitzen diese Eigenschaft der Perspektivierung, vor allem auch solche, die charakteristisch für einen kulturspezifischen Kontext stehen. Zu den Möglichkeiten, die der Einsatz von Metaphern bietet, zählt vor allem der "Highlighting und Hiding"-Effekt (LAKOFF/JOHNSON 1980), indem Metaphern bestimmte Aspekte betonen oder verdunkeln. Um welche es sich dabei im Einzelnen handelt, hängt von mehreren Faktoren ab, wie zum Beispiel der politischen Orientierung von Journalisten oder Politikern oder der wirtschaftlichen Lage eines Landes.
Sprache gehört zu den wesentlichen Aspekten der Interkulturalität. Zuerst wird eine kurze Einführung in die soziolinguistische Interkulturalitätsforschung gegeben, besonders in Hinblick auf interlinguale Strategien als Forschungsfeld. Als theoretischer Rahmen wird der Forschungsansatz des Sprachmanagements vorgestellt, mit dem die Konstruktionsprozesse sprachlicher Verständigung in interkulturellen Situationen auf verschiedenen Ebenen umfassend behandeln werden können. In der Fallstudie geht es um eine deutsch-polnischen Inszenierung von Familie Schroffenstein (Heinrich von Kleist). Die in dieser Inszenierung verwendeten alternativen Strategien wie rezeptive Zweisprachigkeit, Sprachaustausch oder Einbeziehung der weniger verbreiteten Partnersprache weisen neue Anwendungsmöglichkeiten für die deutsche Sprache im mehrsprachigen Kontext auf, die auch in der Forschung und Lehre der interkulturellen Germanistik berücksichtigt werden sollten.
Die linguistic landscapes als alltägliches Phänomen vermitteln neben der unmittelbaren Konfrontation mit der gesellschaftlichen Wirklichkeit auch Einblicke in die spezifischen, kulturell vorstrukturierten Kommunikationssituationen, die auch für den Fremdsprachenunterricht interessante Impulse bieten können. Der Beitrag befasst sich mit den linguistic landscapes als wissenschaftlichem Paradigma in seinen verschiedenen Erscheinungsformen. Besonderes Augenmerk wird dabei auf das aktuelle Paradigma gelegt, das auch für das Forschungsfeld des Fremdsprachenlernens und -lehrens eine erweiterte empirische Basis schafft. Im Anschluss daran wird das sprachdidaktische Potential von Sprachlandschaften fokussiert, indem auf die sprachliche Vielfalt eingegangen wird, die in der Stadt Brünn überall im öffentlichen Raum feststellbar ist. Das Projekt "Linguistic landscapes von Brünn (Brno)" spiegelt nicht nur die Sprachkontakte und die Sprachenpolitik in diesem Raum wider, sondern macht auch die hier ablaufenden Kulturkontakte transparent und zeigt, wie der öffentliche Raum als Diskursplattform genutzt wird.
Potenzial interkultureller Konzeptualisierung und Hermeneutik am Beispiel des Flüchtlingsdiskurses
(2017)
In diesem Beitrag soll untersucht werden, wie die in größtmöglicher Breitenwirkung erzielende Online-Kommunikation deutscher und österreichischer Akteure des politischen Zentrums sowie der politischen Peripherie das Zusammenspiel kultureller Konstellationen im weiteren Sinn innerhalb des Flüchtlingsdiskurses die kulturelle Identität der eigenen bzw. der anderen Bezugsgröße konzeptuell-semiotisch konstruiert und inwieweit kulturelle Unterschiede populistisch oder zum besseren Verständnis der involvierten Kulturen genutzt werden. Dabei soll eine Methode erprobt werden, die einerseits die Einflüsse der kulturellen Konstellationen wie Landes- bzw. Regionalkultur vs. andere Kulturgemeinschaften, jeweiliges Selbstverständnis der drei Gesellschaftssektoren, Organisations- und Gruppenkulturen erfasst sowie ihre Synergie auswertet, andererseits auch die erforderlichen interdisziplinär ausgerichteten hermeneutischen Instrumente definiert.
Der wissenschaftliche Artikel ist eine Textsorte, die weltweit und zahlreich von der scientific community produziert und rezipiert wird. Doch obwohl es sich um eine international bekannte und häufig verwendete Textsorte handelt, zeichnen sich wissenschaftliche Artikel je nach Herkunft und Sprache durch zahlreiche Unterschiede aus. In diesem Beitrag folgt auf eine kurze Darstellung von Unterschieden deutscher und tschechischer wissenschaftlicher Artikel eine kontrastive Betrachtung der Fußnoten innerhalb dieser Texte. Interessant ist diesbezüglich nicht nur, welche unterschiedlichen Typen von Fußnoten in deutschen und tschechischen wissenschaftlichen Artikeln Verwendung finden, sondern auch, inwiefern die sprachlichen Merkmale der Fußnoten denen der Texte selbst entsprechen bzw. von ihnen abweichen.
Thema des vorliegenden Beitrags ist das interaktionale Potenzial des Scherzens in seiner Funktion als kooperativ entfaltete Handlung der Kritik. Im Fokus liegen speziell Kontexte, die als 'interkultureller Dialog' markiert sind und in denen sich die Interaktionsaufgabe stellt, an diskursiven 'kulturellen Grenzen' verständigungsorientiert zu arbeiten. Exemplarisch wird an einer Gesprächssequenz zwischen deutschen und ägyptischen Studierenden gezeigt, wie gerade im gemeinsamen Scherzen Konstruktionen kultureller Zugehörigkeit und Differenz kritisch-konstruktiv bearbeitbar werden, auch in beziehungsorganisatorisch schwierigen Situationen. Als entscheidend erweist sich die damit verbundene Initiierung "kulturellen Handelns". Grundlage der Untersuchung ist ein sprachwissenschaftlicher kritisch-diskursanalytischer Zugang zum Material ('Oldenburger Ansatz' der Kritischen Diskursanalyse), in dessen Rahmen diskurssemantische und interaktionsanalytische Perspektiven zusammengeführt werden.
Zieht man ein Fazit aus den verschiedenen Aspekten der Disziplinen Fremdsprachenerwerb, Musikerziehung und Interkulturelle Erziehung, führt dies zu interdisziplinären Überlegungen darüber, inwieweit sich eine Kooperation miteinander für jeden der Bereiche als sinnvoll erweist bzw. erweisen kann. Musik und Sprache haben sehr viel gemeinsam - beide sind nach einem Regelsystem konstruiert d.h. Wörter und Klänge werden zu größeren funktionellen Einheiten wie Sätzen und Phrasen zusammengefügt. Diese Regelsysteme bestimmen jeweils auch die Beziehungen ihrer einzelnen Teile zum Ganzen und bestimmte Abhängigkeiten der sprachlichen und musikalischen Elemente voneinander. Sie werden vom Menschen durch unbewusste Lernprozesse erworben. Der Beitrag stellt die Ergebnisse einer Studie dar, die an der Pädagogischen Fakultät Hradec Králové durchgeführt wurde und die sich dem Thema Musik im Fremdsprachenunterricht widmet. Es wurden ausgewählte Deutschlehrwerke analysiert und anschließend eine Umfrage unter Fremdsprachenlehrern durchgeführt. Musik im Fremdsprachenunterricht (FSU) zu verwenden, hat ein großes Potenzial. Deshalb sollte sie ein fester Bestandteil in jeder Phase des Fremdsprachenerwerbens sein.
In diesem Beitrag geht es zunächst um den aktuellen Stand der Forschung über das Verhältnis von Sprache und Emotionen mit besonderer Berücksichtigung der Untersuchungen zum Deutschen und Tschechischen. Anschließend werden einige Teilaspekte des Themas behandelt: die Unterscheidung zwischen emotionsausdrückender und emotionsbezeichnender Lexik, die Rolle der bildlichen Sprache sowie das Verhältnis vom Sprachübergreifenden und Einzelsprachlichen bei der Verbalisierung von Emotionen. Abschließend wird der Frage nachgegangen, welche Konsequenzen die im Rahmen eines Projektes ermittelten Gemeinsamkeiten, Ähnlichkeiten und Unterschiede bei der Versprachlichung von Emotionen im Deutschen und Tschechischen für die Behandlung emotionsrelevanter Lexik im DaF-Unterricht bei tschechischen Muttersprachlern haben können.
Beim Gebrauch einer Fremdsprache durch Anfänger handelt es sich offensichtlich um "Spielarten interkultureller Kommunikation" (FÖLDES 2007: 614). Eine bezüglich der arabischen Auslandsgermanistik ergiebige Auseinandersetzung mit der Schreibfertigkeit gelingt erst, wenn interkulturelle und handlungsorientierte Aspekte zusammen und sprachkomparatistisch berücksichtigt werden. Davon ausgehend lässt sich dann erklären, inwieweit mögliche differente Verhaltens- und Handlungsmuster in der deutschen und der arabischen Sprach- bzw. Kulturgemeinschaft das Schreiben in der deutschen Sprache beeinflussen. Neben Faktoren im sprachsystematischen und lexikalisch-semantischen Bereich lässt sich dies im pragmatischen Bereich an zwei Parametern des kommunikativen Verhaltenstyps (Grad der Expressivität sowie der der Ritualisierung) untersuchen. Mögliche differente Verhaltens- bzw. Handlungsweisen werden hier anhand von arabischen Germanistikstudierenden geschriebener Aufsätze bzw. E-Mails diskutiert.
The script of Caryl Churchill’s short play Hot Fudge (like several other plays by this author) contains detailed directions for overlapping conversation. At certain points in the play these may be contributing to a number of effects similar to those described for the naturally occurring ‘collaborative floor’, such as enthusiasm and mutual support. The importance of an interactive approach to constructed conversation is pointed out in the article, particularly that of analysing the overlapped speaker’s response to appreciate the discursive significance of the overlapping turn. For instance, acknowledging and/or reusing the other speaker’s overlapping formulations in a non-oppositional format can show an understanding of these contributions as collaboratively oriented. Therefore, such an interpretation of overlapping dialogue in a dramatic text will affect the reader’s understanding of the interpersonal context (e.g. dominance-seeking/mutual support/collaboration between pairs of speakers). In particular, this approach is taken to show how certain kinds of overlapping similar to those described for the naturally occurring conversation can be used dramatically to supportive rather than conflictive ends. Overall, it is shown how the dramatic characters’ interpersonal orientations become inferable from their use of certain dialogic options.
Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be different, children should always be treated in dedicated pediatric trauma centers. In fact, the vast majority of pediatric patients with blunt splenic trauma can be managed non-operatively. This paper presents the World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines.
Purpose: The aim of this study was to analyze systematically the influence of the relative centrifugation force (RCF) on leukocytes, platelets and growth factor release within fluid platelet-rich fibrin matrices (PRF).
Materials and methods: Systematically using peripheral blood from six healthy volunteers, the RCF was reduced four times for each of the three experimental protocols (I–III) within the spectrum (710–44 g), while maintaining a constant centrifugation time. Flow cytometry was applied to determine the platelets and leukocyte number. The growth factor concentration was quantified 1 and 24 h after clotting using ELISA.
Results: Reducing RCF in accordance with protocol-II (177 g) led to a significantly higher platelets and leukocytes numbers compared to protocol-I (710 g). Protocol-III (44 g) showed a highly significant increase of leukocytes and platelets number in comparison to -I and -II. The growth factors’ concentration of VEGF and TGF-β1 was significantly higher in protocol-II compared to -I, whereas protocol-III exhibited significantly higher growth factor concentration compared to protocols-I and -II. These findings were observed among 1 and 24 h after clotting, as well as the accumulated growth factor concentration over 24 h.
Discussion: Based on the results, it has been demonstrated that it is possible to enrich PRF-based fluid matrices with leukocytes, platelets and growth factors by means of a single alteration of the centrifugation settings within the clinical routine.
Conclusions: We postulate that the so-called low speed centrifugation concept (LSCC) selectively enriches leukocytes, platelets and growth factors within fluid PRF-based matrices. Further studies are needed to evaluate the effect of cell and growth factor enrichment on wound healing and tissue regeneration while comparing blood concentrates gained by high and low RCF.
The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.
Correction to: Nature Communications https://doi.org/10.1038/s41467-017-01045-x, published online 31 October 2017
It has come to our attention that we did not specify whether the stimulation magnitudes we report in this Article are peak amplitudes or peak-to-peak. All references to intensity given in mA in the manuscript refer to peak-to-peak amplitudes, except in Fig. 2, where the model is calibrated to 1 mA peak amplitude, as stated. In the original version of the paper we incorrectly calibrated the computational models to 1 mA peak-to-peak, rather than 1 mA peak amplitude. This means that we divided by a value twice as large as we should have. The correct estimated fields are therefore twice as large as shown in the original Fig. 2 and Supplementary Fig. 11. The corrected figures are now properly calibrated to 1mA peak amplitude. Furthermore, the sentence in the first paragraph of the Results section ‘Intensity ranged from 0.5 to 2.5 mA (current density 0.125–0.625 mA mA/cm2), which is stronger than in previous reports’, should have read ‘Intensity ranged from 0.5 to 2.5 mA peak to peak (peak current density 0.0625–0.3125 mA/cm2), which is stronger than in previous reports.’ These errors do not affect any of the Article’s conclusions. Correct versions of Fig. 2 and Supplementary Fig. 11 are presented below as Figs. 1, 2.
Transcranial electrical stimulation has widespread clinical and research applications, yet its effect on ongoing neural activity in humans is not well established. Previous reports argue that transcranial alternating current stimulation (tACS) can entrain and enhance neural rhythms related to memory, but the evidence from non-invasive recordings has remained inconclusive. Here, we measure endogenous spindle and theta activity intracranially in humans during low-frequency tACS and find no stable entrainment of spindle power during non-REM sleep, nor of theta power during resting wakefulness. As positive controls, we find robust entrainment of spindle activity to endogenous slow-wave activity in 66% of electrodes as well as entrainment to rhythmic noise-burst acoustic stimulation in 14% of electrodes. We conclude that low-frequency tACS at common stimulation intensities neither acutely modulates spindle activity during sleep nor theta activity during waking rest, likely because of the attenuated electrical fields reaching the cortical surface.
Ribosome recycling orchestrated by the ATP binding cassette (ABC) protein ABCE1 can be considered as the final—or the first—step within the cyclic process of protein synthesis, connecting translation termination and mRNA surveillance with re-initiation. An ATP-dependent tweezer-like motion of the nucleotide-binding domains in ABCE1 transfers mechanical energy to the ribosome and tears the ribosome subunits apart. The post-recycling complex (PRC) then re-initiates mRNA translation. Here, we probed the so far unknown architecture of the 1-MDa PRC (40S/30S·ABCE1) by chemical cross-linking and mass spectrometry (XL-MS). Our study reveals ABCE1 bound to the translational factor-binding (GTPase) site with multiple cross-link contacts of the helix–loop–helix motif to the S24e ribosomal protein. Cross-linking of the FeS cluster domain to the ribosomal protein S12 substantiates an extreme lever-arm movement of the FeS cluster domain during ribosome recycling. We were thus able to reconstitute and structurally analyse a key complex in the translational cycle, resembling the link between translation initiation and ribosome recycling.
The endoplasmic reticulum–mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level. Here we report that conserved surface areas on opposite sides of the Mdm10 β-barrel interact with SAM and ERMES, respectively. We generated point mutants to separate protein assembly (SAM) from morphology and phospholipid homeostasis (ERMES). Our study reveals that the β-barrel channel of Mdm10 serves different functions. Mdm10 promotes the biogenesis of α-helical and β-barrel proteins at SAM and functions as integral membrane anchor of ERMES, demonstrating that SAM-mediated protein assembly is distinct from ER-mitochondria contact sites.
In this paper, we study the limit of compactness which is a graph index originally introduced for measuring structural characteristics of hypermedia. Applying compactness to large scale small-world graphs (Mehler, 2008) observed its limit behaviour to be equal 1. The striking question concerning this finding was whether this limit behaviour resulted from the specifics of small-world graphs or was simply an artefact. In this paper, we determine the necessary and sufficient conditions for any sequence of connected graphs resulting in a limit value of CB = 1 which can be generalized with some consideration for the case of disconnected graph classes (Theorem 3). This result can be applied to many well-known classes of connected graphs. Here, we illustrate it by considering four examples. In fact, our proof-theoretical approach allows for quickly obtaining the limit value of compactness for many graph classes sparing computational costs.
Background: To evaluate survival data and local tumor control after transarterial chemoembolization in two groups with different embolization protocols for the treatment of HCC patients.
Methods: Ninty-nine patients (mean age: 63.6 years), 78 male (78.8%) with HCC were repeatedly treated with chemoembolization in 4-week-intervals. Eighty-eight patients had BCLC-Stage-B and in 11 patients, chemoembolization was performed for bridging (BCLC-Stage-A). In total, 667 chemoembolization treatments were performed (mean 6.7 treatments/patient). The administered chemotherapeutic agent included mitomycin. For embolization, lipiodol only (n = 51;51.5%; mean age 63.8 years; 38 male), or lipiodol plus degradable starch microspheres (DSM) (n = 48; 48.5%; mean age 63.4 years; 40 male) were used. The local tumor response was assessed by MRI using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Patient survival times were evaluated using Kaplan-Meier curves and log-rank tests.
Results: The local tumor control in the lipiodol-group was: PR (partial response) in 11 (21.6%), SD (stable disease) in 32 (62.7%) and PD (progressive disease) in 8 cases (15.7%). In the lipiodol-DSM-group, PR was seen in 14 (29.2%), SD in 22 (45.8%), and PD in 12 (25.0%) individuals (p = 0.211). The median survival of patients after chemoembolization with lipiodol was 25 months and in the lipiodol-DSM-group 28 months (p = 0.845).
Conclusion: Our data suggest a slight benefit of the use of lipiodol and DSM in comparison of using lipiodol only for chemoembolization of HCC in terms of local tumor control and survival data, this trend did not reach the level of significance.