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Alternative polyadenylation (APA) is a widespread mechanism that contributes to the sophisticated dynamics of gene regulation. Approximately 50% of all protein-coding human genes harbor multiple polyadenylation (PA) sites; their selective and combinatorial use gives rise to transcript variants with differing length of their 3' untranslated region (3'UTR). Shortened variants escape UTR-mediated regulation by microRNAs (miRNAs), especially in cancer, where global 3'UTR shortening accelerates disease progression, dedifferentiation and proliferation. Here we present APADB, a database of vertebrate PA sites determined by 3' end sequencing, using massive analysis of complementary DNA ends. APADB provides (A)PA sites for coding and non-coding transcripts of human, mouse and chicken genes. For human and mouse, several tissue types, including different cancer specimens, are available. APADB records the loss of predicted miRNA binding sites and visualizes next-generation sequencing reads that support each PA site in a genome browser. The database tables can either be browsed according to organism and tissue or alternatively searched for a gene of interest. APADB is the largest database of APA in human, chicken and mouse. The stored information provides experimental evidence for thousands of PA sites and APA events. APADB combines 3' end sequencing data with prediction algorithms of miRNA binding sites, allowing to further improve prediction algorithms. Current databases lack correct information about 3'UTR lengths, especially for chicken, and APADB provides necessary information to close this gap. Database URL: http://tools.genxpro.net/apadb/
Antigenic and 3D structural characterization of soluble X4 and hybrid X4-R5 HIV-1 Env trimers
(2014)
Background: HIV-1 is decorated with trimeric glycoprotein spikes that enable infection by engaging CD4 and a chemokine coreceptor, either CCR5 or CXCR4. The variable loop 3 (V3) of the HIV-1 envelope protein (Env) is the main determinant for coreceptor usage. The predominant CCR5 using (R5) HIV-1 Env has been intensively studied in function and structure, whereas the trimeric architecture of the less frequent, but more cytopathic CXCR4 using (X4) HIV-1 Env is largely unknown, as are the consequences of sequence changes in and near V3 on antigenicity and trimeric Env structure.
Results: Soluble trimeric gp140 Env constructs were used as immunogenic mimics of the native spikes to analyze their antigenic properties in the context of their overall 3D structure. We generated soluble, uncleaved, gp140 trimers from a prototypic T-cell line-adapted (TCLA) X4 HIV-1 strain (NL4-3) and a hybrid (NL4-3/ADA), in which the V3 spanning region was substituted with that from the primary R5 isolate ADA. Compared to an ADA (R5) gp140, the NL4-3 (X4) construct revealed an overall higher antibody accessibility, which was most pronounced for the CD4 binding site (CD4bs), but also observed for mAbs against CD4 induced (CD4i) epitopes and gp41 mAbs. V3 mAbs showed significant binding differences to the three constructs, which were refined by SPR analysis. Of interest, the NL4-3/ADA construct with the hybrid NL4-3/ADA CD4bs showed impaired CD4 and CD4bs mAb reactivity despite the presence of the essential elements of the CD4bs epitope. We obtained 3D reconstructions of the NL4-3 and the NL4-3/ADA gp140 trimers via electron microscopy and single particle analysis, which indicates that both constructs inherit a propeller-like architecture. The first 3D reconstruction of an Env construct from an X4 TCLA HIV-1 strain reveals an open conformation, in contrast to recently published more closed structures from R5 Env. Exchanging the X4 V3 spanning region for that of R5 ADA did not alter the open Env architecture as deduced from its very similar 3D reconstruction.
Conclusions: 3D EM analysis showed an apparent open trimer configuration of X4 NL4-3 gp140 that is not modified by exchanging the V3 spanning region for R5 ADA.
Background: Oral anticoagulation (OAC) with coumarins and new anticoagulants are highly effective in preventing thromboembolic complications. However, some studies indicate that over- and under-treatment with anticoagulants are fairly common. The aim of this paper is to assess the appropriateness of treatment in patients with a long-term indication for OAC, and to describe the corresponding characteristics of such patients on the basis of screening results from the cluster randomized PICANT trial.
Methods: Randomly selected family practices in the federal state of Hesse, Germany, were visited by study team members. Eligible patients were screened using an anonymous patient list that was generated by the general practitioners? software according to predefined instructions. A documentation sheet was filled in for all screened patients. Eligible patients were classified into 3 categories (1: patients with a long-term indication for OAC and taking anticoagulants, 2: patients with a long-term indication for OAC but not taking anticoagulants, 3: patients without a long-term indication for OAC but taking an anticoagulant on a permanent basis). IBM SPSS Statistics 20 was used for descriptive statistical analysis.
Results: We screened 2,036 randomly selected, potentially eligible patients from 52 family practices. 275 patients could not be assigned to one of the 3 categories and were therefore not considered for analysis. The final study sample comprised 1,761 screened patients, 1,641 of whom belonged to category 1, 78 to category 2, and 42 to category 3. INR values were available for 1,504 patients of whom 1,013 presented INR values within their therapeutic ranges. The majority of screened patients had very good compliance, as assessed by the general practitioner. New antithrombotic drugs were prescribed in 6.1% of cases.
Conclusions: The screening results showed that a high proportion of patients were receiving appropriate anticoagulation therapy. The numbers of patients with a long-term indication for OAC therapy that were not receiving oral anticoagulants, and without a long-term indication that were receiving OAC, were considerably lower than expected. Most patients take coumarins, and the quality of OAC control is reasonably high.
Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME.
Background: Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker.
Methods: Samples of 120 HDV-infected patients recruited in an international multicenter treatment trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA-IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and angiogenetic factors were measured using multiplex technology (Bio-Plex System). A second independent cohort of 78 patients was studied for the development of liver-related clinical endpoints (decompensation, HCC, liver transplantation or death; median follow up of 3.0 years, range 0.6–12).
Results: Anti-HDV IgM serum levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%) patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels, various other antiviral cytokines were negatively associated with anti-HDV IgM. Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05).
Conclusions: Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap marker to determine disease activity in hepatitis delta which has prognostic implications. High anti-HDV IgM levels may indicate an activated interferon system but exhausted antiviral immunity.
The present article analyzes a prominent yet relatively understudied contact space among Native American, New Zealand Maori, and aboriginal Taiwanese literatures: the struggle of indigenous peoples to negotiate optimal relationships between themselves and the natural world, particularly in light of capitalist modernity and globalization. Many indigenous narratives draw sharp distinctions between native peoples and outsiders, predictably portraying the former as protectors and the latter as destroyers of both nature and indigenous local cultures. The Native American Chickasaw writer Linda Hogan's (1947-) novel 'People of the Whale' (2008), the Maori writer Patricia Grace's (1937-) novel 'Patiki' (1986), and the aboriginal Taiwanese writer Topas Tamapima's short story "Zuihou de lieren" are no exception. But these texts also problematize notions of the so-called "ecological native." They do so most conspicuously by revealing the ambiguous relationships those peoples believed closest to nature have with the nonhuman world, that is to say their environmental ambiguity ('ecoambiguity') (Thornber 2012).
Angekommensein ist Unterwegssein : zur Neudeutung der Begriffe 'Flucht' und 'Wohnen' bei Fred Wander
(2014)
Der Aufsatz untersucht die literarisch-philosophischen Voraussetzungen von Fred Wanders Prosaschriften, insbesondere seinen Hotelromanen. Ausgangspunkt des Beitrags ist Wanders Autobiographie 'Das gute Leben' (2006), mit besonderem Augenmerk auf das Adjektiv 'gut' und dessen kontextueller Bedeutung. Sein Verständnis von 'gut' weist auf die Notwendigkeit einer neuen Ethik für die Überlebenden des Naziterrors hin, die sich teils mit Adornos Ethik-Begriff der 'Minima Moralia', teils mit Heideggers Kritik des Humanismus deckt. Vor allem die Begriffe 'Flucht' und 'Wohnen' - bei Wander jeweils als 'gelassenes Ausweichen' ebenso als 'Haus-Hotel-Metapher' dargestellt - tragen zu einer neuen Bestimmung von Wanders Ethik-Begriff bei, die allen Menschen helfen soll, vergangenes und gegenwärtiges Unheil zu überleben.
Anfangen
(2014)
En arche en ho logos, im Anfang war der Logos (Joh 1,1); darüber kann man streiten, insofern es Theologie ist, sagte man aber, es seien die Logiken (oder doch logoi) in den Anfängen, in den methodisch je neuen Versuchen gelegen, so beschriebe man die Morgenröten des Intellekts, die vielleicht auch in präsumptiver Summa und der Spannung das ergeben, was man den Logos nennen könnte. Man beginnt also so: etwa mit einem Wort, das noch ungewiss ist, oder einem Zitat …
Tatsächlich mag es dies sein, was uns Gedichte bis heute bedeutsam macht. In ihnen beginnt etwas, drückt man es so sachlich wie möglich aus, so generieren sie wohl Methoden. Mit einem unsäglichen Wort der Gegenwartspädagogik könnte man sie vorwissenschaftlich heißen.
Wissenschaft verfügt über Methodik, sie setzt sich einem Risiko aus, wenn sie eine neue erfindet, so gewiss auch ist, dass erst die neue Methode - die neue Frage - einen neuen Respons hervorrufen kann. Dieses Vortasten aber ist in Zeiten des Drittmittelfinanzierens und Evaluierens bedroht; und damit womöglich die Forschung nur mehr ein um Perfektibilität ringendes Sich-Wiederholen. Einzig das Kühne in den Versprechen zu Beginn einzelner Projekte erinnert vage an die kühnen Erwartungen der Naturpoesie, als deren Erben man dereinst folglich manche Projektmittelanträge vielleicht entdecken wird …
The present paper deals with inter- and hypertextual relations between two unpublished elegies of the Romanian poet of German origin Anemone Latzina and R M. Rilke’s Duino Elegies. The research aims at uncovering the importance of Rilke as an author of the German Modernity in times of dictatorship, as Rilke’s texts provided trust, hope, courage and strength. So the reception of the German poetry of the Modernity is to be understood both as individual as well as generational.
Background: Emergency ultrasound is gaining importance in medical education. Widespread teaching methods are frontal presentations and hands-on training. The primary goal of our study was to evaluate the impact of frontal presentations (PS) by analysis of retained knowledge rate (RKR) and learning load (LL).
Methods: Our study was conducted during four introductory courses in emergency ultrasound covering Extended Focused Assessment with Sonography for Trauma (E-FAST) and Focused Echocardiography Evaluation in Life Support (FEEL). Standardized PS (length of 10 to 50 min) were presented by experienced trainers, who were asked to provide keywords, key messages, and images and assign a score to each. Group 1 consisted of 11 medical students with no prior ultrasound experience, and group 2 consisted of 80 physicians. Each group was audience to seven to eight standard PS and requested to answer a free text questionnaire after 0 h, 2.5 h, 24 h, and 14 days.
Results: In group 1, 168/176 questionnaires were analyzed, and 161/202 were analyzed in group 2. RKR in group 1 was 32.5%, 15%, 16%, and 12% at 0 h, 2.5 h, 24 h, and 2 weeks. The physicians' RKR were 23%, 20.5%, and 22.4% after 0, 2.5, and 24 h of a respective PS. The LL was 1.6/min for students and 1.2/min for physicians. There was no difference in RKR when comparing PS with higher and lower LL for both groups; shorter or case-based PS were associated with a higher RKR (p < 0.01).
Conclusions: Our study provides evidence that only a limited amount of information can be processed at a time. Only 12% of knowledge is retained after 2 weeks. Presentations of short duration can increase the retained knowledge rate. Therefore, frontal presentations and classroom-based ultrasound training and teaching should be adapted.
The web and the social web play an increasingly important role as an information source for Members of Parliament and their assistants, journalists, political analysts and researchers. It provides important and crucial background information, like reactions to political events and comments made by the general public. The case study presented in this paper is driven by two European parliaments (the Greek and the Austrian parliament) and targets an effective exploration of political web archives. In this paper, we describe semantic technologies deployed to ease the exploration of the archived web and social web content and present evaluation results.
Aus dem Studentenfutter ist die leckere Cashewnuss nicht wegzudenken und manchmal findet sie sich auch auf dem Weihnachtsteller oder im Weihnachtsgebäck. Weniger bekannt sind jedoch die vielfältigen Nutzungsmöglichkeiten, die sich hinter dem exotischen Cashewbaum (auch Kaschubaum, Acajubaum oder Nierenpflanze) verbergen. Und auch eine Cashewblüte oder den sog. Cashewapfel (Kaschuapfel) bekommt man bei uns kaum einmal zu sehen, denn die Art ist hier nur in Botanischen Gärten zu finden und dort fruchtet sie nur selten.
High-throughput metabarcoding studies on fungi and other eukaryotic microorganisms are rapidly becoming more frequent and more complex, requiring researchers to handle ever increasing amounts of raw sequence data. Here, we provide a flexible pipeline for pruning and analyzing fungal barcode (ITS rDNA) data generated as paired-end reads on Illumina MiSeq sequencers. The pipeline presented includes specific steps fine-tuned for ITS, that are mostly missing from pipelines developed for prokaryotes. It (1) employs state of the art programs and follows best practices in fungal high-throughput metabarcoding; (2) consists of modules and scripts easily modifiable by the user to ensure maximum flexibility with regard to specific needs of a project or future methodological developments; and (3) is straightforward to use, also in classroom settings. We provide detailed descriptions and revision techniques for each step, thus giving the user maximum control over data treatment and avoiding a black-box approach. Employing this pipeline will improve and speed up the tedious and error-prone process of cleaning fungal Illumina metabarcoding data.
Background: Anemia is a common condition in the elderly and a significant risk factor for increased morbidity and mortality, reducing not only functional capacity and mobility but also quality of life. Currently, few data are available regarding anemia in hospitalized geriatric patients. Our retrospective study investigated epidemiology and causes of anemia in 405 hospitalized geriatric patients.
Methods: Data analysis was performed using laboratory parameters determined during routine hospital admission procedures (hemoglobin, ferritin, transferrin saturation, C-reactive protein, vitamin B12, folic acid, and creatinine) in addition to medical history and demographics.
Results: Anemia affected approximately two-thirds of subjects. Of 386 patients with recorded hemoglobin values, 66.3% were anemic according to WHO criteria, mostly (85.1%) in a mild form. Anemia was primarily due to iron deficiency (65%), frequently due to underlying chronic infection (62.1%), or of mixed etiology involving a combination of chronic disease and iron deficiency, with absolute iron deficiency playing a comparatively minor role.
Conclusion: Greater awareness of anemia in the elderly is warranted due to its high prevalence and negative effect on outcomes, hospitalization duration, and mortality. Geriatric patients should be routinely screened for anemia and etiological causes of anemia individually assessed to allow timely initiation of appropriate therapy.
Most available knowledge on fungal arginine metabolism is derived from studies on Saccharomyces cerevisiae, in which arginine catabolism is initiated by releasing urea via the arginase reaction. Orthologues of the S. cerevisiae genes encoding the first three enzymes in the arginase pathway were cloned from Kluyveromyces lactis and shown to functionally complement the corresponding deletion in S. cerevisiae. Surprisingly, deletion of the single K. lactis arginase gene KlCAR1 did not completely abolish growth on arginine as nitrogen source. Growth rate of the deletion mutant strongly increased during serial transfer in shake-flask cultures. A combination of RNAseq-based transcriptome analysis and 13C-15N-based flux analysis was used to elucidate the arginase-independent pathway. Isotopic 13C15N-enrichment in γ-aminobutyrate revealed succinate as the entry point in the TCA cycle of the alternative pathway. Transcript analysis combined with enzyme activity measurements indicated increased expression in the Klcar1Δ mutant of a guanidinobutyrase (EC.3.5.3.7), a key enzyme in a new pathway for arginine degradation. Expression of the K. lactis KLLA0F27995g (renamed KlGBU1) encoding guanidinobutyrase enabled S. cerevisiae to use guanidinobutyrate as sole nitrogen source and its deletion in K. lactis almost completely abolish growth on this nitrogen source. Phylogenetic analysis suggests that this enzyme activity is widespread in fungi.
The abundance of humpback whales occurring around Boa Vista, Cape Verde Islands, was estimated by markrecapture modelling. Photographs of markings on tail flukes of individual whales were collected during the breeding season. Sighting histories were constructed for each individual and an abundance of 171 animals was estimated using a Jolly-Seber mark-recapture model. Correcting for known biases arising due to sex-specific behaviour and temporary emigration insofar as possible, an estimate of 260 whales was obtained. This is significantly higher than the previous estimate of 99 humpback whales from this region. Due to limited survey effort it is not known how representative the study area is of the entire Cape Verde archipelago and this estimate may be considered to be biased low and serves as a minimum estimate. The high recapture probability (0.37) coupled with the low abundance is consistent with a small local population. The low survival rate (0.86) suggests possible emigration and further studies are needed to assess connectivity between humpback whales breeding in Cape Verde and other breeding locations. The amount of exchange between groups of whales breeding in Cape Verde and adjacent areas remains unknown. It is unclear whether the abundance estimate herein applies to part of an isolated population or part of a larger and continuous one.
The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.
Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25–10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.
Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia
(2014)
Background: Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death.
Methods: We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm−/−).
Results: ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm−/− mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed.
Conclusions: Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.
This paper deals with the control exerted by the mitochondrial translocator FLX1, which catalyzes the movement of the redox cofactor FAD across the mitochondrial membrane, on the efficiency of ATP production, ROS homeostasis, and lifespan of S. cerevisiae. The deletion of the FLX1 gene resulted in respiration-deficient and small-colony phenotype accompanied by a significant ATP shortage and ROS unbalance in glycerol-grown cells. Moreover, the flx1Δ strain showed H2O2 hypersensitivity and decreased lifespan. The impaired biochemical phenotype found in the flx1Δ strain might be justified by an altered expression of the flavoprotein subunit of succinate dehydrogenase, a key enzyme in bioenergetics and cell regulation. A search for possible cis-acting consensus motifs in the regulatory region upstream SDH1-ORF revealed a dozen of upstream motifs that might respond to induced metabolic changes by altering the expression of Flx1p. Among these motifs, two are present in the regulatory region of genes encoding proteins involved in flavin homeostasis. This is the first evidence that the mitochondrial flavin cofactor status is involved in controlling the lifespan of yeasts, maybe by changing the cellular succinate level. This is not the only case in which the homeostasis of redox cofactors underlies complex phenotypical behaviours, as lifespan in yeasts.
Das Ziel dieses Beitrags ist, die Vita einer fast in Vergessenheit geratenen Literatin, Maria Therese von Artner, darzustellen. Ihre Lebensgeschichte und literarisches Schaffen sind für slowakische Germanisten mindestens aus zwei Gründen interessant. Erstens verbrachte sie ein Teil ihres Lebens mit in den Komitaten Neutra (Nitra) und Trentschin (Trenčín), zweitens wurde sie von Zeitgenossen als eine talentierte Dichterin wahrgenommen und zählt zugleich zu den wenigen bekannten deutsch schreibenden Schriftstellerinnen des frühen 19. Jahrhunderts unserer Region...
O presente texto lida com a forma do juízo em Hölderlin e Hegel, focalizando principalmente seus momentos de divisão e unificação. Inicialmente, unificação e divisão são aqui tratadas a partir de temáticas desenvolvidas em torno do amor no séc. XVIII. O juízo é analisado basicamente no âmbito da Ciência da lógica, de Hegel, de prefácios do romance Hyperion e do texto "Juízo e Ser", de Hölderlin. A análise visa expor as passagens entre esses momentos do juízo nos textos supracitados, as quais mobilizam relações entre singular, particular e geral. Considerando essas relações, propõe-se uma interpretação do romance acima mencionado.
Aktuelle Berichte
(2014)
Repräsentationen der verlorenen Heimat in der deutschsprachigen Literatur Böhmens, Mährens und Schlesiens. Internationale Tagung in Vitoria-Gasteiz, 27.-29. Juni 2013
Transnationale Repräsentationen von Flucht und Vertreibung der Deutschen nach dem Zweiten Weltkrieg (Deutschland - Polen - Tschechien - Slowakei). Internationale Tagung an der Universität Lille 3, 20.–22. März 2014
"Ende einer Ära. 1914 in den Literaturen der Donaumonarchie und ihrer Nachfolgestaaten". 22. Franz Werfel-StipentiatInnen-Tagung in Wien, 28.–29. März 2014
Projekt SpoluRosteme :: ZusammenWachsen :: 30 Jahre GFPS-Geschichte im Kontext der gesellschaftlichen Entwicklung in Mittel- und Osteuropa. Internationales Seminar in Ústí nad Labem, 3.–6. April 2014
Zentren und Peripherien. Deutsch und seine interkulturellen Beziehungen in Mitteleuropa. Sektion: "Macht und Ohnmacht. Hegemonialität und Marginalität in den Literaturen Mitteleuropas". IV. Kongress des MGV in Erfurt, 10.–12. April 2014
Eine "Nomadisierung der Moderne"? Interdisziplinäre Perspektiven der Interkulturalitätsforschung. Internationale Tagung am Internationalen Forschungszentrum Chamisso-Literatur an der Universität München, 26.–28. Juni 2014
"Deutsch ohne Grenzen". Tagung des Germanistenverbandes der Tschechischen Republik in České Budějovice, 16.–18. September 2014
Frieden und Krieg im mitteleuropäischen Raum. Historisches Gedächtnis und literarische Reflexion. Kolloquium der Österreich-Bibliotheken im Ausland. Tschechische Republik, 20.−27. September 2014
U ovome radu autor će, na osnovu vlastitih istraživanja, pokušati dati sumaran prikaz akcenatskih svojstava govora otoka Iža, smještenog u zadarskom arhipelagu. Namjera mu je smjestiti iški govor i akcenatski sustav među drugim čakavskim otočkim govorima, dati fonetski i fonološki opis pojedinih akcenata i potkrijepiti ih primjerima koje je čuo od iških govornika i, konačno, pokušati utvrditi fonološki status čakavskog akuta u iškome govoru. Budući da su istraživanja bila ograničenoga karaktera, ovaj rad nije zamišljen kao konačan opis, već kao polažišna točka za buduća istraživanja koja je potrebno izvršiti na osnovu kojih će se moći napraviti što iscrpniji i potpuniji opis iškoga govora i akcenatskoga sustava.
"Wie so oft, war es auch in Ihrem Falle leichter, Unrecht zu tun, als dieses Unrecht wieder gutzumachen." Mit dieser bitteren Bemerkung fasste im Oktober 1957 der Dekan der Wirtschafts- und Sozialwissenschaftlichen Fakultät, der Ökonom Prof. Dr. Hans Möller, in einem Entschuldigungsschreiben an Walter Braeuer ein Rehabilitierungsverfahren zusammen, das bereits mehr als zehn Jahre zuvor im Januar 1946 gestartet war.
Im Folgenden soll kurz geklärt werden, was Genus ist (Kap. 2) und – auch wenn diese Frage nicht mit unserem derzeitigen Wissen beantwortbar ist – woher Genus kommen könnte (Kap. 3). Hauptsächlich stellt sich jedoch die Frage: Was tun mit Genus, das heute das Endstadium einer langen Grammatikalisierung darstellt (Kap. 4)? Hier wird die wichtigste Antwort lauten: Genus hat eine neue, eine syntaktische Nutzung erfahren, indem es maßgeblich daran beteiligt ist, unsere berühmten Nominalklammern zu bauen (4.1). Außerdem gibt es weitere "Recyclingmöglichkeiten" von Genus, nämlich: a) Objekte, die Namen tragen, zu klassifizieren (die Kaiser Wilhelm), b) Beziehungen zwischen namentragenden und namenverwendenden Personen zu qualifizieren (der Peterle, das Anna) oder sogar c) Personen zu degradieren (das Merkel). Mit Punkt a) begebe ich mich in die Onomastik, mit Punkt b) in die Dialektologie, und mit Punkt c) werde ich mit der Genderlinguistik enden.
Background: Chronic particulate matter (PM) exposure is correlated to various health effects, even at low amounts. WHO has defined PM concentration limits as daily and annual mean values which were made legally binding in the European Union. While many studies have focused on PM concentrations in special environments, little is known about the average PM- exposure for both employees and passengers in the German public transportation system.
Methods: Particulate matter (PM10, PM2.5, PM1) - concentrations were monitored for 30 minutes at 15 different areas in Frankfurt am Main with major public traffic. Maximum and mean concentrations and, as a surrogate for the inhaled dosage, the Area Under the Curve (AUC) for 15 minutes of exposure were calculated.
Results: The WHO limits for PM10 and PM2.5 were exceeded at nearly all times and areas. Highest maximum concentrations were found at underground stations, subterranean railway stations and subterranean shopping arcades with much lower values obtained at surface points. In one measurement at a surface test point smokers who neglected the non-smoking policy could be identified as a major cause for a at least temporary strong increase of PM-load as seen in high maximum values and normal averages.
Conclusions: Subterranean areas have high particulate matter contamination exceeding WHO limits. Improvement may be achieved by increased ventilation. Subterranean shops and kiosks, being workplaces with long term exposure, should be equipped with external air supply. The non- smoking policy of the "Deutsche Bahn" for public spaces should be enforced.
Background: Multimorbidity is a common phenomenon in primary care. Until now, no clinical guidelines for multimorbidity exist. For the development of these guidelines, it is necessary to know whether or not patients are aware of their diseases and to what extent they agree with their doctor. The objectives of this paper are to analyze the agreement of self-reported and general practitioner-reported chronic conditions among multimorbid patients in primary care, and to discover which patient characteristics are associated with positive agreement.
Methods: The MultiCare Cohort Study is a multicenter, prospective, observational cohort study of 3,189 multimorbid patients, ages 65 to 85. Data was collected in personal interviews with patients and GPs. The prevalence proportions for 32 diagnosis groups, kappa coefficients and proportions of specific agreement were calculated in order to examine the agreement of patient self-reported and general practitioner-reported chronic conditions. Logistic regression models were calculated to analyze which patient characteristics can be associated with positive agreement.
Results: We identified four chronic conditions with good agreement (e.g. diabetes mellitus κ = 0.80;PA = 0,87), seven with moderate agreement (e.g. cerebral ischemia/chronic stroke κ = 0.55;PA = 0.60), seventeen with fair agreement (e.g. cardiac insufficiency κ = 0.24;PA = 0.36) and four with poor agreement (e.g. gynecological problems κ = 0.05;PA = 0.10).Factors associated with positive agreement concerning different chronic diseases were sex, age, education, income, disease count, depression, EQ VAS score and nursing care dependency. For example: Women had higher odds ratios for positive agreement with their GP regarding osteoporosis (OR = 7.16). The odds ratios for positive agreement increase with increasing multimorbidity in almost all of the observed chronic conditions (OR = 1.22-2.41).
Conclusions: For multimorbidity research, the knowledge of diseases with high disagreement levels between the patients' perceived illnesses and their physicians' reports is important. The analysis shows that different patient characteristics have an impact on the agreement. Findings from this study should be included in the development of clinical guidelines for multimorbidity aiming to optimize health care. Further research is needed to identify more reasons for disagreement and their consequences in health care.
Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development.
Immunotherapy of cancer utilizes dendritic cells (DCs) for antigen presentation and the induction of tumor-specific immune responses. However, the therapeutic induction of anti-tumor immunity is limited by tumor escape mechanisms. In this study, immortalized dendritic D2SC/1 cells were transduced with a mutated version of the p53 tumor suppressor gene, p53M234I, or p53C132F/E168G, which are overexpressed in MethA fibrosarcoma tumor cells. In addition, D2SC/1 cells were fused with MethA tumor cells to generate a vaccine that potentially expresses a large repertoire of tumor-antigens. Cellular vaccines were transplanted onto Balb/c mice and MethA tumor growth and anti-tumor immune responses were examined in vaccinated animals. D2SC/1-p53M234I and D2SC/1-p53C132F/E168G cells induced strong therapeutic and protective MethA tumor immunity upon transplantation in Balb/c mice. However, in a fraction of immunized mice MethA tumor growth resumed after an extended latency period. Analysis of these tumors indicated loss of p53 expression. Mice, pre-treated with fusion hybrids generated from D2SC/1 and MethA tumor cells, suppressed MethA tumor growth and averted adaptive immune escape. Polyclonal B-cell responses directed against various MethA tumor proteins could be detected in the sera of D2SC/1-MethA inoculated mice. Athymic nude mice and Balb/c mice depleted of CD4(+) or CD8(+) T-cells were not protected against MethA tumor cell growth after immunization with D2SC/1-MethA hybrids. Our results highlight a potential drawback of cancer immunotherapy by demonstrating that the induction of a specific anti-tumor response favors the acquisition of tumor phenotypes promoting immune evasion. In contrast, the application of DC/tumor cell fusion hybrids prevents adaptive immune escape by a T-cell dependent mechanism and provides a simple strategy for personalized anti-cancer treatment without the need of selectively priming the host immune system.
BACKGROUND: Transient episodes of ischemia in a remote organ or tissue (remote ischemic preconditioning, RIPC) can attenuate myocardial injury. Myocardial damage is associated with tissue remodeling and the matrix metalloproteinases 2 and 9 (MMP-2/9) are crucially involved in these events. Here we investigated the effects of RIPC on the activities of heart tissue MMP-2/9 and their correlation with serum concentrations of cardiac troponin T (cTnT), a marker for myocardial damage.
METHODS: In cardiosurgical patients with cardiopulmonary bypass (CPB) RIPC was induced by four 5 minute cycles of upper limb ischemia/reperfusion. Cardiac tissue was obtained before as well as after CPB and serum cTnT concentrations were measured. Tissue derived from control patients (N = 17) with high cTnT concentrations (≥0.32 ng/ml) and RIPC patients (N = 18) with low cTnT (≤0.32 ng/ml) was subjected to gelatin zymography to quantify MMP-2/9 activities.
RESULTS: In cardiac biopsies obtained before CPB, activities of MMP-2/9 were attenuated in the RIPC group (MMP-2: Control, 1.13 ± 0.13 a.u.; RIPC, 0.71 ± 0.12 a.u.; P < 0.05. MMP-9: Control, 1.50 ± 0.16 a.u.; RIPC, 0.87 ± 0.14 a.u.; P < 0.01), while activities of the pro-MMPs were not altered (P > 0.05). In cardiac biopsies taken after CPB activities of pro- and active MMP-2/9 were not different between the groups (P > 0.05). Spearman's rank tests showed that MMP-2/9 activities in cardiac tissue obtained before CPB were positively correlated with postoperative cTnT serum levels (MMP-2, P = 0.016; MMP-9, P = 0.015).
CONCLUSIONS: Activities of MMP-2/9 in cardiac tissue obtained before CPB are attenuated by RIPC and are positively correlated with serum concentrations of cTnT. MMPs may represent potential targets for RIPC mediated cardioprotection.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00877305.
Acacia pendula, Weeping Myall, (family Fabaceae) is the most legislatively protected plant species in the New South Wales Hunter Valley. Under the NSW Threatened Species Conservation Act 1995 it is listed as an Endangered Population (in the Hunter Valley) and as a component of two Endangered Ecological Communities (one in the Hunter, one elsewhere in NSW); it is also listed as a Critically Endangered Ecological Community (in the Hunter Valley) on the Commonwealth Environment Protection and Biodiversity Conservation Act 1999 and listed as threatened in three other eastern Australian States.
To ascertain the likely original distribution of stands of Acacia pendula in the Hunter Valley, this paper examines the writings of early Australian explorers, herbarium and database records, and the species habitat attributes across NSW. None of the journals examined, including those of botanist/explorer Allan Cunningham (who originally collected Acacia pendula from the Lachlan River in 1817), Thomas Mitchell or Ludwig Leichhardt, make note of the species for the Hunter Valley. Several explorers do, however, record Acacia pendula regularly (>100 times) across other parts of NSW, Queensland, and South Australia.
Historical herbarium and database records show a paucity of records from the Hunter prior to the year 2000, after which a 37-fold increase in observations since 1951 is apparent. For the first 128 years of botanical exploration (1823 to 1951), there are no validated collections or records of Acacia pendula from the Hunter Valley. The single exception is a specimen collected by Cunningham from 1825 (lodged at Kew, UK), purported to be from ‘Hunters River’, but which is morphologically different to other collections of Acacia pendula from that time. There is some uncertainty over the origins of this specimen.
Analysis of habitats supporting Acacia pendula in NSW outside of the Hunter show them to differ significantly in geological age, soil type, rainfall and elevation from those in the Hunter.
Collectively, these findings provide a strong circumstantial case that Acacia pendula was absent from the Hunter at the time of European settlement; this has important implications for the conservation and management of Hunter stands. Rather than being a threatened species in the Hunter Valley, it is postulated that Acacia pendula has been intentionally and/or accidentally introduced to the region, and may now be imposing a new and emerging threat to the endangered grassy woodlands and forests there. There is now an urgent need for genetic studies to clarify the origins of the current Hunter Valley stands, and to define the taxonomic limits of Acacia pendula and its close relatives.
Este artigo recapitula as traduções de Wilhelm Busch publicadas no Brasil e aponta que determinadas circunstâncias de publicação levaram a uma recepção unilateral de sua obra exclusivamente como literatura infantil nesse país. Entre outras estratégias que poderiam estender para uma faixa etária adulta o público leitor da poesia humorística buschiana, propõe-se que o Knittelvers seja traduzido para o português como decassílabo iâmbico. Uma tradução anotada do poema "Hänsel und Gretel" nesse padrão métrico-acentual testa em que medida a escolha consciente de um ritmo e o aproveitamento de associações culturais desencadeadas por ele podem destacar o efeito irônico desse pseudoconto-de-fada.
Based on a meta-analysis, Redick and Lindsey (2013) found that complex span and n-back tasks show an average correlation of r = 0.20, and concluded that "complex span and n-back tasks cannot be used interchangeably as working memory measures in research applications" (p. 1102). Here, we comment on this conclusion from a psychometric perspective. In addition to construct variance, performance on a test contains measurement error, task-specific variance, and paradigm-specific variance. Hence, low correlations among dissimilar indicators do not provide strong evidence for the existence, or absence, of a construct common to both indicators. One way to arrive at such evidence is to fit hierarchical latent factors that model task-specific, paradigm-specific, and construct variance. We report analyses for 101 younger and 103 older adults who worked on nine different working memory tasks. The data are consistent with a hierarchical model of working memory, according to which both complex span and n-back tasks are valid indicators of working memory. The working memory factor predicts 71% of the variance in a factor of reasoning among younger adults (83% for among older adults). When the working memory factor was restricted to any possible triplet of working memory tasks, the correlation between working memory and reasoning was inversely related to the average magnitude of the correlations among the indicators, indicating that more highly intercorrelated indicators may provide poorer coverage of the construct space. We stress the need to go beyond specific tasks and paradigms when studying higher-order cognitive constructs, such as working memory.
CD4+CD25+ regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of the CD4 molecule that is not recognized by other anti-CD4 mAbs. We found that, due to this special epitope binding, BT-061 induces a unique phosphorylation of T-cell receptor complex-associated signaling molecules. This is sufficient to activate the function of Tregs without activating effector T cells. Furthermore, BT-061 does not induce the release of pro-inflammatory cytokines. These results demonstrate that BT-061 stimulation via the CD4 receptor is able to induce T-cell receptor-independent activation of Tregs. Selective activation of Tregs via CD4 is a promising approach for the treatment of autoimmune diseases where insufficient Treg activity has been described. Clinical investigation of this new approach is currently ongoing.
We explore the parameter space of the two-flavor thermal quark–meson model and its Polyakov loop-extended version under the influence of a constant external magnetic field B. We investigate the behavior of the pseudo critical temperature for chiral symmetry breaking taking into account the likely dependence of two parameters on the magnetic field: the Yukawa quark–meson coupling and the parameter T0 of the Polyakov loop potential. Under the constraints that magnetic catalysis is realized at zero temperature and the chiral transition at B=0 is a crossover, we find that the quark–meson model leads to thermal magnetic catalysis for the whole allowed parameter space, in contrast to the present picture stemming from lattice QCD.
Orientation: Publishing methodologically sound, empirically based studies in reputable accredited scientific journals are essential in order to advance knowledge and evidence-based practice in the field of industrial and organisational psychology.
Research purpose: The purpose of the research was to conduct a broad content analysis of the articles published in the South African Journal of Industrial Psychology (SAJIP) between 2004 and 2013. The study aimed to provide a descriptive overview of the most frequent content themes,published authors and institutions, research approaches, strategies, designs and analysis techniques, software packages and sample sizes in industrial and organisational (I-O) psychology utilised in the publications.
Motivation for study: The periodic analyses of published content in scholarly journals provide an index of the extent to which the publications reflect the scope of practice in a given discipline and broaden insight into the direction and relevance of research published in a journal.
Research design, approach and method: A broad systematic content analysis was conducted of 342 documented articles published in the SAJIP between 2004 and 2013. Descriptive data(frequencies and percentages) were used to report the findings.
Main findings: The publishing pattern of the SAJIP appeared to correspond with its focus and scope. Manuscripts utilising mostly cross-sectional quantitative correlational research designs with large samples (n > 201) were published in the SAJIP. The University of Johannesburg and Professor Sebastiaan (Ian) Rothmann were the largest contributors to publications between 2004 and 2013. Organisational psychology and psychometrics were the most prominent domains in I-O psychology research. Data were predominantly processed utilising SPSS.
Practical implications: The insights derived from the findings can be employed to plan future research initiatives in the field of I-O psychology.
Contribution/value-add: The findings provide valuable insight into the current status of the foci of I-O psychology research as published in the SAJIP between 2004 and 2013 and the contribution made by the SAJIP to advancing knowledge and evidence-based practice in I-O psychology.
O trabalho pretende discutir o duplo caráter das obras de arte a partir da obra de Theodor W. Adorno. Pretende-se examinar os argumentos sustentados pelo autor sobre o caráter social das obras, principalmente, no caso da música, em que se pode percebercomo o desenvolvimento do próprio material musical expressa as aporias encontradas na sociedade. Por meio de uma crítica dialética, modo pelo qual as obras de arte respondem às contradições da sociedade, colocando-se, assim, como força de resistência à reificação, quanto a influência negativa que sofrem, porexemplo, no contexto da indústria cultural. Além disso, o artigo pretende se dedicar à reflexão sobre a autonomia das obras de arte, qualidade que as mantém fechadas, desenvolvendo-se apenas segundo leis formais internas, sem que atendam a uma função social. É nesse sentido quese coloca a exigência de uma determinada forma de recepção dasobras, orientada não pela fruição, mas pela possibilidade de interpretar seu teor de verdade. Assim, a dialética presente no modo como as obras se relacionam com a sociedade torna possível concebê-las como possibilidade de crítica à realidade e de resistência à reificação.
The ground beetle genus Cymindis is the most species rich amongst genera in the carabid subtribe Cymindidina (tribe Lebiini). Four subgenera are often recognized, i.e. Cymindis (sensu stricto) Latreille, Afrotarus Jeannel, Taridius Chaudoir and Pinacodera Schaum. Cymindis (sensu stricto) has a predominately Holarctic distribution (Hunting 2013) and includes Cymindis alutacea Wollaston, C. dohrnii Wollaston and C. anchomenoides Wollaston (the last one sometimes placed in Tarulus Bedel, either ranked as a genus or a subgenus), all three endemic to the Cape Verde Islands (Geisthardt 1988, 1996).
Ribosome biogenesis in yeast requires 75 small nucleolar RNAs (snoRNAs) and a myriad of cofactors for processing, modification, and folding of the ribosomal RNAs (rRNAs). For the 19 RNA helicases implicated in ribosome synthesis, their sites of action and molecular functions have largely remained unknown. Here, we have used UV cross-linking and analysis of cDNA (CRAC) to reveal the pre-rRNA binding sites of the RNA helicase Rok1, which is involved in early small subunit biogenesis. Several contact sites were identified in the 18S rRNA sequence, which interestingly all cluster in the “foot” region of the small ribosomal subunit. These include a major binding site in the eukaryotic expansion segment ES6, where Rok1 is required for release of the snR30 snoRNA. Rok1 directly contacts snR30 and other snoRNAs required for pre-rRNA processing. Using cross-linking, ligation and sequencing of hybrids (CLASH) we identified several novel pre-rRNA base-pairing sites for the snoRNAs snR30, snR10, U3, and U14, which cluster in the expansion segments of the 18S rRNA. Our data suggest that these snoRNAs bridge interactions between the expansion segments, thereby forming an extensive interaction network that likely promotes pre-rRNA maturation and folding in early pre-ribosomal complexes and establishes long-range rRNA interactions during ribosome synthesis.
Background: According to current taxonomy only three out of 27 Sinohimalayan leaf warbler species (Phylloscopidae) are considered genetically uniform across their entire breeding range along the Southeastern margin of the Qinghai-Tibetan Plateau, the Buff-barred Warbler (Phylloscopus pulcher) being one of them. Because marked differentiation among Himalayan and Chinese populations has been recently demonstrated for a number of Phylloscopus species (or sister species) we investigated the intraspecific variation of a mitochondrial gene, songs and morphology of P. pulcher in a phylogeographic approach.
Methods: We sequenced a fragment of the mitochondrial cytochrome b, reconstructed haplotype networks and analyzed DNA polymorphism among Himalayan and Chinese populations. We measured time and frequency parameters of two distinct song types and analyzed among population-differentiation in a principal component analysis and a discriminant analysis. We also compared measurements of body size dimensions taken from museum specimens.
Results: The mitochondrial haplotype network (cytb) was divided into two distinct clusters corresponding to geographic origin of samples. Pairwise genetic distances among Himalayan and Chinese mtDNA lineages account for 1.3% which coincides with Pleistocene lineage separation at roughly 650,000 years ago. Genetic diversity is slightly higher in the Chinese part of the species’ range with respect to haplotype and nucleotide diversity while the less diversified Himalayan population lineage shows signs of recent range expansion. The vocal repertoire of P. pulcher comprises two distinct verse types that are combined with short interspersed click notes to long continuous song displays. Trill verse types showed significant differences among regions in almost all measured frequency and time parameters: Chinese males displayed more rapid and more broad-banded trills at a lower pitch. In contrast, warbling verse types showed a distinctively different structure among regions: Himalayan songs consisted of repeated syllables while Chinese songs comprised repetitions of single, long and strongly modulated elements. Subtle morphological differences among specimens from the two study regions could only be confirmed for plumage coloration but not for metric characters.
Conclusions: Based on the genetic and bioacoustic distinctiveness of Chinese Buff-barred Warbler populations, we recommend that the name Phylloscopus pulcher vegetus Bangs, 1913 should be re-validated for this taxon.
A versatile synthetic procedure is described to prepare the benzimidazole-fused 1,2,4-thiadiazoles 2a–c via a methanesulfonyl chloride initiated multistep cyclization involving the intramolecular reaction of an in-situ generated carbodiimide with a thiourea unit. The structure of the intricate heterocycle 2a was confirmed by single-crystal X-ray analysis and its mechanism of formation supported by DFT computations.
Background: A discontinuous dose response relationship is a major characteristic of the anti-inflammatory effects of low-dose X-irradiation therapy. Although recent data indicate an involvement of a variety of molecular mechanisms in these characteristics, the impact of reactive oxygen species (ROS) production to give rise or contribute to these phenomena in endothelial cells (EC) remains elusive.
Material and methods: HUVEC derived immortalized EA.hy926 cells were stimulated by tumor necrosis factor-α (TNF-α, 20 ng/ml) 4 h before irradiation with doses ranging from 0.3 to 1 Gy. To analyse DNA repair capacity, phospho-histone H2AX foci were assayed at 1 h, 4 h and 24 h after irradiation. ROS production and superoxide dismutase (SOD) activity were analysed by fluorometric 2',7'-dichlorodihydrofluorescein-diacetate (H2DCFDA) and colorimetric assays. A functional impact of ROS on γH2AX production was analysed by treatment with the scavenger N-acetyl-L-cysteine (NAC).
Results: Irrespective of stimulation by TNF-α, EA.hy926 cells revealed a linear dose response characteristic of γH2AX foci detection at 1 h and 4 h after irradiation. By contrast, we observed a discontinuity in residual γH2AX foci detection at 24 h after irradiation with locally elevated values following a 0.5 Gy exposure that was abolished by inhibition of ROS by NAC. Moreover, SOD protein expression was significantly decreased at doses of 0.5 Gy and 0.7 Gy concomitant with a reduced SOD activity.
Conclusion: These data implicate a non-linear regulation of ROS production and SOD activity in EA.hy926 EC following irradiation with doses < 1 Gy that may contribute to a discontinuous dose-response relationship of residual γH2AX foci detection.
Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.
Neurons of the mammalian neocortex are produced by proliferating cells located in the ventricular zone (VZ) lining the lateral ventricles. This is a complex and sequential process, requiring precise control of cell cycle progression, fate commitment and differentiation. We have analyzed publicly available databases from mouse and human to identify candidate genes that are potentially involved in regulating early neocortical development and neurogenesis. We used a mouse in situ hybridization dataset (The Allen Institute for Brain Science) to identify 13 genes (Cdon, Celsr1, Dbi, E2f5, Eomes, Hmgn2, Neurog2, Notch1, Pcnt, Sox3, Ssrp1, Tead2, Tgif2) with high correlation of expression in the proliferating cells of the VZ of the neocortex at early stages of development (E15.5). We generated a similar human brain network using microarray and RNA-seq data (BrainSpan Atlas) and identified 407 genes with high expression in the developing human VZ and subventricular zone (SVZ) at 8–9 post-conception weeks. Seven of the human genes were also present in the mouse VZ network. The human and mouse networks were extended using available genetic and proteomic datasets through GeneMANIA. A gene ontology search of the mouse and human networks indicated that many of the genes are involved in the cell cycle, DNA replication, mitosis and transcriptional regulation. The reported involvement of Cdon, Celsr1, Dbi, Eomes, Neurog2, Notch1, Pcnt, Sox3, Tead2, and Tgif2 in neural development or diseases resulting from the disruption of neurogenesis validates these candidate genes. Taken together, our knowledge-based discovery method has validated the involvement of many genes already known to be involved in neocortical development and extended the potential number of genes by 100's, many of which are involved in functions related to cell proliferation but others of which are potential candidates for involvement in the regulation of neocortical development.
Reintroductions of plant species are increasingly popular in conservation practice. Steppe grasslands contain many rare and endangered plant species that are potential objects for such reintroductions. Most reintroduction projects, however, can only target a restricted number of species, which raises the question of how species should be prioritised. Here, we present a method to select priority species for reintroduction based on species' characteristics that are widely used in conservation practice. We first determined the local species pool containing those vascular plant species that occurred both in our target region (Thuringia, Germany) and target habitat (steppe grasslands), yielding 369 species. With the help of an a priori filter that selected currently endangered species with limited distribution, 136 potential target species were determined. These potential target species had experienced stronger decline, had a narrower phytosociological amplitude and were more likely to be species of the Festuco-Brometea class and the Festucetalia valesiacae order than non-target species. Potential target species were then ranked by a points system based on ten conservation-relevant characteristics of the species from the categories "threat and protection status", "distribution and decline", and "habitat affiliation". In the ranking, six steppe grassland plant species (Astragalus exscapus, Bothriochloa ischaemum, Prunella laciniata, Pulsatilla pratensis subsp. nigricans, Scorzonera purpurea, and Seseli hippomarathrum) achieved the highest scores. An additional seven species not specifically characteristic for steppe grasslands also scored highly. A post hoc evaluation of these 13 highest scoring species based on additional conservation criteria left five species (Astragalus exscapus, Linum leonii, Orchis morio, Pulsatilla pratensis subsp. nigricans and Scorzonera purpurea) as species with highest priority for reintroductions and another five species as highly suitable for reintroductions. Associations between the ranking order and different ranking criteria revealed that a species’ threat and rarity in Thuringia and its protection status had the highest representation in the ranking, followed by threat in Germany, regional decline and habitat affiliation. In contrast, international threat and responsibility of Thuringia for its conservation had only low representation in the ranking, probably because these characteristics applied to only a few species. The ranking list gives a selection of species for reintroductions, which combined with additional information based on comprehensive local and floristic knowledge, allows the identification of the species with the highest priority. Our method can be transferred to other regions or habitat types.
O objetivo principal deste artigo é apresentar uma visão geral dos resultados obtidos em uma pesquisa empírica envolvendo aprendizes adultos de alemão como língua estrangeira com conhecimentos prévios de inglês. O foco deste artigo recai sobre os processos envolvidos no ensino/aprendizagem de terceiras línguas, levando-se em consideração que a língua alemã é comumente aprendida como uma segunda língua estrangeira após o inglês. Os principais questionamentos da pesquisa estão baseados em processos de transferência positiva, bem como na interferência linguística observada em um grupo de 50 aprendizes de alemão dos níveis A1 a B1 do Quadro Europeu Comum de Referência para as Línguas. Ao que concerne a relação entre as línguas alemã e inglesa, a afirmação de que o inglês exerce um papel importante na aprendizagem de alemão pôde ser confirmada, sendo o parentesco etimológico entre as duas línguas um dos mais importantes fatores para se determinar a ocorrência de influência interlinguística. Por outro lado, a interferência linguística resultante da coexistência de ambas as línguas demanda o desenvolvimento de uma didática do plurilinguismo que compreenda métodos alternativos para o ensino/aprendizagem de alemão como segunda língua estrangeira no Brasil.
Irrigation intensifies land use by increasing crop yield but also impacts water resources. It affects water and energy balances and consequently the microclimate in irrigated regions. Therefore, knowledge of the extent of irrigated land is important for hydrological and crop modelling, global change research, and assessments of resource use and management. Information on the historical evolution of irrigated lands is limited. The new global Historical Irrigation Dataset (HID) provides estimates of the temporal development of the area equipped for irrigation (AEI) between 1900 and 2005 at 5 arc-minute resolution. We collected subnational irrigation statistics from various sources and found that the global extent of AEI increased from 63 million ha (Mha) in 1900 to 112 Mha in 1950 and 306 Mha in 2005. We developed eight gridded versions of time series of AEI by combining subnational irrigation statistics with different data sets on the historical extent of cropland and pasture. Different rules were applied to maximize consistency of the gridded products to subnational irrigation statistics or to historical cropland and pasture data sets. The HID reflects very well the spatial patterns of irrigated land in the western United States as shown on historical maps. Mean aridity on irrigated land increased and river discharge decreased from 1900–1950 whereas aridity decreased from 1950–2005. The dataset and its documentation are made available in an open data repository at https://mygeohub.org/publications/8 (doi:10.13019/M2MW2G).
BACKGROUND: Acetogenic bacteria are able to use CO2 as terminal electron acceptor of an anaerobic respiration, thereby producing acetate with electrons coming from H2. Due to this feature, acetogens came into focus as platforms to produce biocommodities from waste gases such as H2+CO2 and/or CO. A prerequisite for metabolic engineering is a detailed understanding of the mechanisms of ATP synthesis and electron-transfer reactions to ensure redox homeostasis. Acetogenesis involves the reduction of CO2 to acetate via soluble enzymes and is coupled to energy conservation by a chemiosmotic mechanism. The membrane-bound module, acting as an ion pump, was of special interest for decades and recently, an Rnf complex was shown to couple electron flow from reduced ferredoxin to NAD+ with the export of Na+ in Acetobacterium woodii. However, not all acetogens have rnf genes in their genome. In order to gain further insights into energy conservation of non-Rnf-containing, thermophilic acetogens, we sequenced the genome of Thermoanaerobacter kivui.
RESULTS: The genome of Thermoanaerobacter kivui comprises 2.9 Mbp with a G+C content of 35% and 2,378 protein encoding orfs. Neither autotrophic growth nor acetate formation from H2+CO2 was dependent on Na+ and acetate formation was inhibited by a protonophore, indicating that H+ is used as coupling ion for primary bioenergetics. This is consistent with the finding that the c subunit of the F1FO ATP synthase does not have the conserved Na+ binding motif. A search for potential H+-translocating, membrane-bound protein complexes revealed genes potentially encoding two different proton-reducing, energy-conserving hydrogenases (Ech).
CONCLUSIONS: The thermophilic acetogen T. kivui does not use Na+ but H+ for chemiosmotic ATP synthesis. It does not contain cytochromes and the electrochemical proton gradient is most likely established by an energy-conserving hydrogenase (Ech). Its thermophilic nature and the efficient conversion of H2+CO2 make T. kivui an interesting acetogen to be used for the production of biocommodities in industrial micobiology. Furthermore, our experimental data as well as the increasing number of sequenced genomes of acetogenic bacteria supported the new classification of acetogens into two groups: Rnf- and Ech-containing acetogens.