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The neutron capture cross section of some unstable nuclei is especially relevant for s-process nucleosynthesis studies. This magnitude is crucial to determine the local abundance pattern, which can yield valuable information of the s-process stellar environment. In this work we describe the neutron capture (n,γ) measurement on two of these nuclei of interest, 204Tl and 171Tm, from target production to the final measurement, performed successfully at the n_TOF facility at CERN in 2014 and 2015. Preliminary results on the ongoing experimental data analysis will also be shown. These results include the first ever experimental observation of capture resonances for these two nuclei.
On February 20 at the Max Planck Institut für europäische Rechtsgeschichte, the Legal Historian and member of the Constitutional Court of Peru, Dr. Carlos Ramos Núñez, presented a crucial intervention on the problems that face the current constitutionalism in Latin America. Faced with a heterogeneous group of historians, philosophers and theoreticians of law, interested in the vicissitudes of Latin American juridical evolution, the political-juridical tensions of the Peruvian present served him as a framework to raise various constitutional problems and controversies. ...
A group of Amazonian harvestmen is recognized and described as Amazochroma gen. nov. This taxon includes Discocyrtus carvalhoi Mello-Leitão, 1941 (type species), the only species of Discocyrtus previously thought to occur in Amazonia, and Amazochroma pedroi gen. et sp. nov., described here from the Brazilian states of Acre and Rondônia. New records are added for Amazochroma carvalhoi gen. et comb. nov, expanding its distribution from the Brazilian state of Mato Grosso northwards also to Pará and Amazonas in Brazil and additionally French Guiana and Suriname. Diagnostic features of Amazochroma gen. nov. include: trichromatic pattern of legs, dry marks on the dorsal scutum and base of legs and diastema in the row of macrosetae C of the penis ventral plate. A morphological maximum parsimony analysis (1022 scorings; 16 taxa; 64 characters) is performed to test whether Amazochroma gen. nov. is a member of Discocyrtus and if the traditional allocation of Discocyrtus in Pachylinae is defendable. A clade is retrieved containing three groups: Amazochroma carvalhoi gen. et comb. nov, here described as a new subfamily of Gonyleptidae - Roeweriinae subfam. nov. Discocyrtanus Roewer, 1929 and Roeweria Mello-Leitão, 1923 are accordingly here transferred from Pachylinae to Roeweriinae subfam. nov.
Religious Conversion: An African Perspective includes a selection of key texts which are not easily accessible elsewhere. Most of the chapters discuss the long-standing thesis of Robin Horton who argues that religious change results from social transformation. The contributors provide different perspectives on what remains an ongoing provocative, though inconclusive debate. The book has chapters on conversion in Africa from such authorities as Robin Horton, Humphrey Fisher, and Richard Gray. It also contains chapters on Zambia by Elizaebeth Colson, Brendan Carmody, Austin Cheyeka, Felix Phiri and W Van Binsbergen. This collection of chapters provides an introduction to the discussion surrounding the query: Did the Christian and Muslim messages bring something fundamentally new to the African religious horizon? What has indigenisation meant? What is the role of traditional religion?
Taxonomic revision of Brasiloniscus (Oniscidea, Pudeoniscidae) with description of a new species
(2018)
The Neotropical genus Brasiloniscus, erected by Lemos de Castro (1973), is revised and validated herein. The genus was originally described including two species, B. maculatus and B. verrucosus, but no type species was designated. According to § 13 of ICZN (1999) the name of the genus is therefore unavailable. Both species are redescribed, and B. maculatus is designated as the type species of the genus. The genus name will thus be available for the systematics of Oniscidea. In addition, a new species, B. littoralis gen. et sp. nov., is described based on material from the Brazilian Atlantic Forest from the state of Rio de Janeiro.
Ambrosia artemisiifolia (common ragweed) is an invasive species native to North America and was accidentally introduced to Europe in the 19th century. Widespread in disturbed habitats, it is a major weed in spring-sown crops and it causes serious allergic rhinitis and asthma due to its allergenic pollen. The aim of this research was to analyse the effects of both competitive vegetation and herbivory by Ophraella communa to control A. artemisiifolia in an agricultural area of north-western Italy. Hayseed mixtures, both over-seeded over the resident plant community or after ploughing, when seeded before the winter season, were able to suppress the establishment of A. artemisiifolia as well as to reduce its growth in terms of plant height and inflorescence size. Defoliation of A. artemisiifolia by O. communa at the end of the growing season was conspicuous but most of the plants still produced flowers and seeds. However, significant O. communa attack was recorded for reproductive structures. As for non-target species, O. communa was mainly recorded on Asteraceae, with low density and low degree of damage. Reduction of inflorescence size due to competitive vegetation and damage to male flowers by O. communa may diminish the amount of available pollen. The results of this study may be useful for the implementation of management measures to control A. artemisiifolia in agricultural areas using mixtures of native species.
En este estudio se describen dos nuevas especies de hemípteros del género Aleuropleurocelus (Hemiptera: Aleyrodidae): Aleuropleurocelus mexicanus Carapia y Sánchez sp. nov., encontrada en los estados de Coahuila, México, Puebla, Sonora, y Tlaxcala en hojas de Quercus agrifolia Née y Quercus sp., y Aleuropleurocelus anahuac Carapia y Sánchez sp. nov. encontrada en los estados de México, Morelos y Puebla en el envés de hojas de Quercus. Se proporcionan microfotografías de estructuras morfológicas de puparios y se discute la separación con otras especies ovales de Aleuropleurocelus.
n this contribution we lay down a lattice setup that allows for the nonperturbative study of a field theoretical model where a SU(2) fermion doublet, subjected to non-Abelian gauge interactions, is also coupled to a complex scalar field doublet via a Yukawa and an “irrelevant” Wilson-like term. Using naive fermions in quenched approximation and based on the renormalizedWard identities induced by purely fermionic chiral transformations, lattice observables are discussed that enable: a) in theWigner phase, the determinations of the critical Yukawa coupling value where the purely fermionic chiral transformation become a symmetry up to lattice artifacts; b) in the Nambu-Goldstone phase of the resulting critical theory, a stringent test of the actual generation of a fermion mass term of non-perturbative origin. A soft twisted fermion mass term is introduced to circumvent the problem of exceptional configurations, and observables are then calculated in the limit of vanishing twisted mass.
Testing a non-perturbative mechanism for elementary fermion mass generation: numerical results
(2018)
Based on a recent proposal according to which elementary particle masses could be generated by a non-perturbative dynamical phenomenon, alternative to the Higgs mechanism, we carry out lattice simulations of a model where a non-abelian strongly interacting fermion doublet is also coupled to a doublet of complex scalar fields via a Yukawa and an “irrelevant" Wilson-like term. In this pioneering study we use naive fermions and work in the quenched approximation. We present preliminary numerical results both in the Wigner and in the Nambu-Goldstone phase, focusing on the observables relevant to check the occurrence of the conjectured dynamical fermion mass generation effect in the continuum limit of the critical theory in its spontaneously broken phase.
Robust predictions of alien species richness are useful to assess global biodiversity change. Nevertheless, the capacity to predict spatial patterns of alien species richness remains largely unassessed. Using 22 data sets of alien species richness from diverse taxonomic groups and covering various parts of the world, we evaluated whether different statistical models were able to provide useful predictions of absolute and relative alien species richness, as a function of explanatory variables representing geographical, environmental and socio-economic factors. Five state-of-the-art count data modelling techniques were used and compared: Poisson and negative binomial generalised linear models (GLMs), multivariate adaptive regression splines (MARS), random forests (RF) and boosted regression trees (BRT). We found that predictions of absolute alien species richness had a low to moderate accuracy in the region where the models were developed and a consistently poor accuracy in new regions. Predictions of relative richness performed in a superior manner in both geographical settings, but still were not good. Flexible tree ensembles-type techniques (RF and BRT) were shown to be significantly better in modelling alien species richness than parametric linear models (such as GLM), despite the latter being more commonly applied for this purpose. Importantly, the poor spatial transferability of models also warrants caution in assuming the generality of the relationships they identify, e.g. by applying projections under future scenario conditions. Ultimately, our results strongly suggest that predictability of spatial variation in richness of alien species richness is limited. The somewhat more robust ability to rank regions according to the number of aliens they have (i.e. relative richness), suggests that models of aliens species richness may be useful for prioritising and comparing regions, but not for predicting exact species numbers.
Anomiopus cirulito Cano n. sp., from the tropical forest of the Mayan Biosphere Reserve, Petén, Guatemala is described. This is the northernmost known species of the genus Anomiopus Westwood (Coleoptera: Scarabaeidae: Scarabaeinae) and is related to the Costa Rican and Panamanian Anomiopus panamensis (Paulian).
Autosomal recessive Ataxia Telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the Ataxia-Telangiectasia-Mutated (ATM) gene, a serine-threonine protein kinase involved in DNA-damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood.
Im Folgenden werden die Freiheit der Person, vornehmlich das Recht auf Habeas Corpus, mithin der Schutz gegen willkürliche Inhaftierungen und die Freiheit des Eigentums, so wie sie in der Paulskirche konzipiert wurden, in Betracht gezogen. Die Vorgehensweise wird vor allem rechtsphilosophisch bzw. analytisch sein: Zunächst werden die jeweiligen Artikel und Paragraphen der Erklärung der Paulskirchenverfassung erörtert, in welchen die respektiven Grundrechte aufgebaut werden. Anschließend werden sie mit den entsprechenden Vorschriften anderer Grund- und Menschenrechtskatalogen verglichen, insbesondere mit den Verfassungen der süddeutschen Staaten, mit der Französischen Erklärung von 1789, mit der Allgemeinen Erklärung der Menschenrechte von 1948 und mit dem heutigen deutschen Grundgesetz. Hie und da wird gelegentlich auch auf relevante historische Ereignisse und prägende Literatur Bezug genommen, wobei dies den eigentlichen Gegenstand der derzeitigen Untersuchung nicht ausmacht.
Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation and accumulation of immature myeloblasts, which impair normal hematopoiesis. While this definition categorizes the disease into a distinctive group, the large number of different genetic and epigenetic alterations actually suggests that AML is not a single disease, but a plethora of malignancies. Still, most AML patients are not treated with targeted medication but rather by uniform approaches such as chemotherapy. The identification of novel treatment options likely requires the identification of cancer cell vulnerabilities that take into account the different genetic and epigenetic make-up of the individual tumors. Here we show that STK3 depletion by knock-down, knock-out or chemical inhibition results in apoptotic cells death in some but not all AML cell lines and primary cells tested. This effect is mediated by a premature activation of cyclin dependent kinase 1 (CDK1) in presence of elevated cyclin B1 levels. The anti-leukemic effects seen in both bulk and progenitor AML cells suggests that STK3 might be a promising target in a subset of AML patients.
Following a taxonomic revision of Begonia L. (Begoniaceae, Cucurbitales) from Northeast India based on 332 herbarium specimens, 38 species are confirmed to occur in the region, of which ten are endemic. One new species is described, Begonia koelzii R.Camfield sp. nov., in B. sect. Platycentrum (Klotzsch) A.DC. One species is reduced into synonymy; B. barbata Wall. is now a synonym of B. thomsonii A.DC. Three species, B. difformis (Irmsch.) W.C.Leong, C.I Peng & K.F.Chung, B. labordei H.Lév. and B. handelii Irmsch., are reported new for India, and B. lushaiensis C.E.C.Fisch. is reinstated as an accepted species, having previously been synonymised under B. modestiflora Kurz. A key to the species in the region and preliminary conservation assessments are presented.
A taxonomic revision of Panamanian species of the genus Dasymutilla Ashmead (Hymenoptera, Mutillidae) is presented and a key for the six species is given, all recognized from both sexes. Dasymutilla colorado Cambra, Williams and Quintero sp. nov., from central and eastern Panama, is described and illustrated. Sex associations permitted us to make the following five synonymies: D. sleipniri Manley and Pitts, 2007 (male) under D. phya (Cameron, 1895) (female); D. deyrollesi Mickel, 1937 (male) and Sphaerophthama [sic.] temaxensis Cameron, 1895 under Dasymutilla araneoides (Smith, 1862) (female); D. ionothorax Manley and Pitts, 2007 (male) under Dasymutilla spilota Manley and Pitts, 2007 (female); and D. guanacaste Manley and Pitts, 2007 (male) under D. paradoxa (Gerstaecker, 1874) (female). Seasonal flight activity for Dasymutilla from six years of continuous malaise trappings in Barro Colorado Island is presented.
Eu busco neste artigo mostrar alguns aspectos relativos a diferentes pesquisas e reflexões que empreendi em anos recentes sobre o conceito de indústria cultural. A questão central é o pensamento de Theodor W. Adorno com especial atenção para a atualidade de sua dialética negativa. Minha intervenção acerca da atualidade do conceito de indústria cultural possui três passos argumentativos: o entrelaçamento entre racionalidade e dominação como a base de uma teoria da sociedade em Adorno; algumas mudanças no capitalismo contemporâneo e suas implicações para um conceito de indústria cultural no século XXI e; a posição da indústria cultural no contexto da Sociologia brasileira. O objetivo central do artigo, produzido na forma de ensaio, é enfatizar a atualidade da teoria crítica da sociedade de Theodor Adorno mediante argumentos específicos ao campo da Sociologia.
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).
Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate this modality of innate immunity. To this end, EVs were isolated from interferon-stimulated macrophage cultures or from serum of patients with acute or chronic hepatitis C. EVs were characterized by electron microscopy, flow cytometry, RNA-sequencing, and Western blot analysis. The effect of EVs on replication of HCV was assessed in coculture models. Functional analyses were performed to assess the impact of PUFAs on EV-mediated antiviral immunity. We found that macrophages secreted various cytokines shortly after stimulation with type I and II IFN, which orchestrated a fast but short-lasting antiviral state. This rapid innate immune answer was followed by the production of macrophage-derived EVs, which induced a late, but long-lasting inhibitory effect on HCV replication. Of note, exposure of macrophages to PUFAs, which are important regulators of immune responses, dampened EV-mediated antiviral immune responses. Finally, EVs from patients with hepatitis C exhibited long-lasting antiviral activities during IFN therapy as well. The antiviral effect of EVs from Caucasian and Japanese patients differed, which may be explained by different nutritional uptake of PUFAs. In conclusion, our data indicate that macrophage-derived EVs mediate long-lasting inhibitory effects on HCV replication, which may bridge the time until efficient adaptive immune responses are established, and which can be blunted by PUFAs.
Lizards of Paraguay: an integrative approach to solve taxonomic problems in central South America
(2018)
Paraguay is located in the center of South America with drier and warmer climatic conditions in the western part of the country, and more temperate and humid in the eastern region. Biogeographically, Paraguay is a key spot in South America, where several ecoregions converge. In my study, I sampled most of the ecoregions of Paraguay. The main objective of my work is to solve taxonomic problems, identified through genetic barcoding analyses, in the central region of South America. To achieve this objective, I used selected taxa of the Paraguayan Squamata as models taking into consideration the crucial geographic position of the country, plus the scarce available genetic data of Paraguayan reptiles.
The collecting activities were performed in the framework of a barcoding inventory project of the Paraguayan herpetofauna and carried out mostly in rural areas searching for animals in different types of habitats using active search as the sampling technique.
For genetics, the extraction of DNA was performed with DNeasy® Blood & Tissue Kit of Qiagen® for sets of few samples, and the fiber glass plate protocol for sets of 96 samples. I assessed the quality of sequences after amplification in agarose gel electrophoresis. The first marker sequenced was 16S mtDNA, used for barcoding analysis. A DNA barcode is a genetic identifier for a species. Once a taxonomic problem was detected, I generate more gene sequences to target the issue.
All the analyses to test phylogenetic hypotheses (based on single genes or concatenated datasets) were performed under Maximum Likelihood and Bayesian approaches. To root the phylogenetic trees, I chose the available taxon (or taxa) most closely related to the respective studied group as outgroups. For the general tree of Paraguayan Squamata, based on barcodes of 16S, I chose Sphenodon punctatus.
I generated a total of 142 sequences of 64 species of Squamata from Paraguay (Appendix I). The final alignment of 615 bp comprised 249 samples. The best substitution model for the Barcoding dataset based on the gene 16S was GTR+G, according to the BIC.
To complement molecular evidence generated with the ML grouping of 16S barcodes, I took a morphological approach based on voucher specimens collected during fieldwork (usually the same specimens that I used for genetic analysis), supplemented by the revision of museum collections.
Summarizing my results, samples of Colobosaura exhibit large genetic distances, and accordingly I revalidated Colobosaura kraepelini (Appendix II). Tropidurus of the spinulosus group show two clades and among them there is little genetic and morphological variation, I synonymized T. tarara and T. teyumirim with T. lagunablanca, and T. guarani with T. spinulosus (Appendix III). I detected the presence of candidate species of Homonota, and I restricted the name H. horrida for Argentina, and described two new species of Homonota (Appendices IV and V), and a new species of Phyllopezus also in the Family Phyllodactylidae (Appendix VI).
In this work I present the most comprehensive analysis of genetic samples of Squamata from Paraguay. The results obtained here will be useful to help to clarify further taxonomic issues regarding the squamate fauna from the central region of South America. Moreover, the data generated for this study will have a positive impact in a larger geographic context, beyond Paraguayan borders.
Regarding the conservation of the Paraguayan reptiles, and considering the taxonomic changes accomplished here, it is important to note that many species lack legal protection. In Paraguay, the major problem for conservation is habitat loss due to extensive crop farming. Thus, currently, the protected areas are the best strategy for conservation of biodiversity in the country. However, many such areas face legal problems (e.g., lack of official measurements, management plans, forest guards, infrastructure, etc.) so that the maintenance of their biodiversity over time is not guaranteed.
In conclusion, in this study I present contributions on the taxonomy of mostly lizards from Paraguay. Due to lack of samples, I was not able to deal with a deep taxonomic revision of the country's snakes. Based on my results, I can argue that analyses of Xenodontini and Pseudoboini are currently a pressing research issue. This barcoding project may continue since some colleagues in Paraguay are interested in collaboration. Given that the sequenced specimens are yet a small portion of the actual diversity of Paraguay, it will be of utmost importance to continue and expand these studies that will further improve our taxonomic knowledge. Furthermore, it is desirable to have Paraguayan scientists not only involved, but to see them taking the lead of high quality taxonomic research.
The gecko genus Phyllopezus is distributed mainly along South America’s "Dry Diagonal" (Caatinga, Cerrado, and Chaco). The genus has been the subject of recent taxonomic analyses and includes four described species and seven candidate species referred to here as Phyllopezus pollicaris sensu lato. In Paraguay, Phyllopezus is known from the Chaco and Cerrado where it is abundant, and also from a small isolated population from a rocky hill formation named "Cordillera de Los Altos" (Los Altos mountain range). Here we analyzed genetic samples from across its range, including new samples from Paraguay, using DNA barcoding analysis of the mitochondrial 16S gene and phylogenetic analyses using both Bayesian and Maximum Likelihood methods. We found genetic and morphological differences among geckos from the Los Altos mountain range and the remaining Phyllopezus populations. Using both molecular and morphological evidence we describe a new Phyllopezus species, sister to P. przewalskii. Genetic differentiation among described and putative Phyllopezus species is greater than their morphological differences, which likely accounts for these cryptic taxa remaining undescribed for so long.
Complex I (proton-pumping NADH:ubiquinone oxidoreductase) is the largest enzyme of the mitochondrial respiratory chain and a significant source of reactive oxygen species (ROS). We hypothesized that during energy conversion by complex I, electron transfer onto ubiquinone triggers the concerted rearrangement of three protein loops of subunits ND1, ND3, and 49-kDa thereby generating the power-stoke driving proton pumping. Here we show that fixing loop TMH1-2ND3 to the nearby subunit PSST via a disulfide bridge introduced by site-directed mutagenesis reversibly disengages proton pumping without impairing ubiquinone reduction, inhibitor binding or the Active/Deactive transition. The X-ray structure of mutant complex I indicates that the disulfide bridge immobilizes but does not displace the tip of loop TMH1-2ND3. We conclude that movement of loop TMH1-2ND3 located at the ubiquinone-binding pocket is required to drive proton pumping corroborating one of the central predictions of our model for the mechanism of energy conversion by complex I proposed earlier.
Purpose: Acute kidney injury (AKI) is a severe complication in medical and surgical intensive care units accounting for a high morbidity and mortality. Incidence, risk factors, and prognostic impact of this deleterious condition are well established in this setting. Data concerning the neurocritically ill patients is scarce. Therefore, aim of this study was to determine the incidence of AKI and elucidate risk factors in this special population.
Methods: Patients admitted to a specialized neurocritical care unit between 2005 and 2011 with a length of stay above 48 hours were analyzed retrospectively for incidence, cause, and outcome of AKI (AKI Network-stage ≥2).
Results: The study population comprised 681 neurocritically ill patients from a mixed neurosurgical and neurological intensive care unit. The prevalence of chronic kidney disease (CKD) was 8.4% (57/681). Overall incidence of AKI was 11.6% with 36 (45.6%) patients developing dialysis-requiring AKI. Sepsis was the main cause of AKI in nearly 50% of patients. Acute kidney injury and renal replacement therapy are independent predictors of worse outcome (hazard ratio [HR]: 3.704; 95% confidence interval [CI]: 1.867-7.350; P < .001; and HR: 2.848; CI: 1.301-6.325; P = .009). Chronic kidney disease was the strongest independent risk factor (odds ratio: 12.473; CI: 5.944-26.172; P < .001), whereas surgical intervention or contrast agents were not associated with AKI.
Conclusions: Acute kidney injury in neurocritical care has a high incidence and is a crucial risk factor for mortality independently of the underlying neurocritical condition. Sepsis is the main cause of AKI in this setting. Therefore, careful prevention of infectious complications and considering CKD in treatment decisions may lower the incidence of AKI and hereby improve outcome in neurocritical care.
A typical characteristic of Central German dialects, especially of the Ripuarian dialect, is that it has collective nouns with ge- + -ze (cf. gesteinze) besides those with ge- + -e (cf. gesteine) corresponding to Dutch gesteente and gestene. A relationship between ge- + -ze and ge- + -te has been assumed for a long time. A corpus-based comparison is given in order to explain the genesis of these different formation types (ge- + -e, ge- + -ze, ge- + -te) and their relations. It seems likely that earlier Dutch formations influenced their Ripuarian counterparts. Rarely, the circumfix ge- + -te also occurs in Ripuarian texts and may be autochthone. One main result is that the suffic -ze in Ripuarian restores the collective formation in the circumfix ge- + -e when it was destroyed by the e-apokope. This is a rare instance where an element of word formation is replaced by another one in order to neutralize the isolation effect of sound change.
Wie sich Konzessivkonnektoren im 18. und 19. Jh. entwickelt haben, untersuchen Lisa Bürgerhoff, Jana Giesenschlag, Linda Kunow und Alexandra Kern für ihren Beitrag "Von ob ich schon wanderte zu obschon ich wanderte?! - Eine Korpusuntersuchung zur Konzessivität von 1700-1900". Ihre Untersuchungen im Deutschen Textarchiv zeigen unter anderem einen Zusammenhang zwischen der Zusammenschreibung der Konnektoren und einer eindeutig konzessiven Lesart, der für obschon, obgleich, obwohl und obzwar allerdings unterschiedlich stark ist. Auch die Faktizität der Teilsätze und das Auftreten verstärkender Partikeln sind für die Entwicklung der ob-Gruppe von Bedeutung. Als eindeutigste und frequenteste Konzessivkonnektoren stellen sich insgesamt obwohl und vor allem obzwar heraus.
Although modern biologics targeting different inflammatory mediators show promising therapeutic success, comprehensive knowledge about the molecular events in psoriatic keratinocytes that contribute to the pathogenesis and could serve as therapeutic targets is still scarce. However, recent efforts to understand the deregulated signal transduction pathways have led to the development of small molecule inhibitors e.g., tofacitinib targeting the Jak/Stat cascade that opens additional therapeutic options. Recently, the PI3-K/Akt/mTOR signaling pathway has emerged as an important player in the control of epidermal homeostasis. This review summarizes the current knowledge on the role of this pathway in the pathogenesis of psoriasis, especially the epidermal manifestation of the disease and discusses current approaches to target the pathway therapeutically.
Depiction verbs such as paint license i(mage)- and p(ortrait)-readings; for instance, Ben painted a cow can convey that Ben produced an image of an unspecific cow or a portrait of a specific cow. This paper takes issue with a property-based intensional analysis of depiction verbs (Zimmermann, 2006b, 2016) and instead argues for an extensional account. Accordingly, the i-reading is rooted in the introduction of worldly representations by the explicit noun cow as such, whereas the p-reading is rooted in the interpolation of an implicit representation via coercion. This take on the ambiguity captures the following key traits. On i-readings, only representations are accessible to quantifiers and anaphors; moreover, intensional effects such as substitution failure disappear once ordinary objects and representations are adequately distinguished. P-readings, by contrast, involve representations that depend on the portrayed ordinary objects as particulars; correspondingly, only ordinary objects are accessible to quantifiers and anaphors. The proposal is spelled out in Asher’s (2011) Type Composition Logic.
We propose a unified framework to measure the effects of different reforms of the pension system on retirement ages and macroeconomic indicators in the face of demographic change. A rich overlapping generations (OLG) model is built and endogenous retirement decisions are explicitly modeled within a public pension system. Heterogeneity with respect to consumption preferences, wage profiles, and survival rates is embedded in the model. Besides the expected direct effects of these reforms on the behavior of households, we observe that feedback effects do occur. Results suggest that individual retirement decisions are strongly influenced by numerous incentives produced by the pension system and macroeconomic variables, such as the statutory eligibility age, adjustment rates, the presence of a replacement rate, and interest rates. Those decisions, in turn, have several impacts on the macro-economy which can create feedback cycles working through equilibrium effects on interest rates and wages. Taken together, these reform scenarios have strong implications for the sustainability of pension systems. Because of the rich nature of our unified model framework, we are able to rank the reform proposals according to several individual and macroeconomic measures, thereby providing important support for policy recommendations on pension systems.
Im Rahmen eines Monitorings wurden alle im Artenhilfskonzept der BVNH von 1999 ermittelten sowie einzelne später bekannt gewordene hessische Vorkommen der Aufrechten Weißmiere im Frühjahr 2016 erneut aufgesucht und dokumentiert. Von diesen 27 Vorkommen konnten wir lediglich 15 bestätigen. Für einen großen Teil der untersuchten Populationen sind erhebliche Rückgänge der Individuenzahlen zu verzeichnen, lediglich vier Vorkommen sind stabil geblieben oder sogar leicht angestiegen. Bei der Interpretation der Individuenzahlen ist jedoch zu berücksichtigen, dass die Art mit großen witterungsbedingten Schwankungen der Populationsgröße auftritt und jahrweise auch völlig ausbleiben kann. Die Beobachtungen bestätigen eine akute Bedrohung durch das Brachfallen oder die Unterbeweidung der Wuchsorte und die damit verbundenen Folgeerscheinungen wie das Ausbleiben der durch den Viehtritt verursachten Offenböden oder die zunehmende Gehölzausbreitung. Der auf den Flächen entstehende Altgras- und Moosfilz verhindert mutmaßlich ein Auskeimen der Art. Als wesentliche Voraussetzung für die Erhaltung und langfristige Sicherung der Vorkommen der Aufrechten Weißmiere wird die Beibehaltung oder Wiedereinführung einer extensiven Nutzung angesehen. Neben einer Beweidung mit Schafen scheint sich auch eine extensive Rinderbeweidung günstig auf die Populationen auszuwirken. Um den Fortbestand der Art in Hessen zu sichern, sind auch Wiederansiedlungen von Moenchia erecta an erloschenen Wuchsorten in Betracht zu ziehen, sofern eine geregelte Folgenutzung in Form einer Beweidung gewährleistet ist.
Vorhofflimmern entsteht unter anderem durch ein Ungleichgewicht zwischen sympathischem und parasympathischem autonomen Nervensystem. Sowohl invasive Ansätze via Ablation oder Denervierung als auch minimalinvasive Ansätze via Elektrostimulation liefern erfolgsversprechende Ergebnisse in Bezug auf Beeinflussung eines bestehenden Vorhofflimmerns.
Interessanterweise konnte durch Akupunktur des Tragus eine Reduktion von Vorhofflimmer-Rezidiven nach Kardioversion erreicht werden. Ziel dieser Studie war die Evaluation von Akupunktur-induzierten kardialen (vegetativen) Effekten bei gesunden Probanden.
Herzgesunde männliche Probanden (n=24) wurden im Bereich des Vagus-Innervationsgebietes an der Concha inferior des Ohres (Herzpunkt 100, OHR) sowie an einem klassischen Akupunktur-Punkt des Herzens (ventralen Unterarm, P6/Neiguan, ARM) akupunktiert. Eine „Placebo“-Akupunktur eines Punktes, der gegen Gonarthrose-Schmerzen helfen soll (Magenpunkt 35), diente als Kontrolle. Die Hälfte der Probanden erhielt eine zusätzliche Messung ohne Akupunktur, um Effekte durch das alleinige Platzieren einer Nadel zu untersuchen.
Um eine Aktivierung des ANS zu bewirken und Veränderungen quantifizieren zu können, wurden 12-Kanal Langzeit-EKG Messungen wie folgt durchgeführt: 30 Minuten (min) in liegender Position unter Akupunktur, Entfernung der Akupunkturnadel, 5 min liegend, 5 min sitzend, 5 min stehend, 5 min sitzend.
Es erfolgten Analysen folgender Parameter der Herzfrequenzvariabilität: Herzfrequenz, SDNN, RMSSD, HF, LF, LF/HF. Des Weiteren wurden Periodic Dynamics Repolarization und Deceleration Capacity untersucht.
Verglichen mit Placebo-Akupunktur wurde sowohl durch Akupunktur am OHR als auch am ARM die Herzfrequenz in liegender und sitzender Körperpositionen signifikant gesenkt (Phasen 30L, 5S1, 5S2, ∆5L-5S1, ∆5S1-5ST).
Während die Akupunktur am OHR vor allem die SDNN signifikant erhöhte, führte die Akupunktur am ARM zu einer signifikanten Steigerung von RMSSD und dem parasympathischen Leistungsdichtespektrum-Parameter HF. Der Quotient LF/HF wurde ebenfalls signifikant gesenkt.
Kein Unterschied bestand zwischen Placebo-Akupunktur und Messung ohne Akupunktur, sodass postuliert werden kann, dass das alleinige Platzieren einer Nadel keinen nennenswerten Effekt auf das autonome Nervensystem besitzt.
Die Ergebnisse der Studie zeigen, dass eine Akupunktur an Orten, die mit dem autonomen Nervensystem verschaltet sind, zu einer Modulation des parasympathischen kardialen autonomen Nervensystems führen kann.
Eine Modulation der parasympathisch-sympathischen Balance durch minimalinvasive Zusatzbehandlung, wie in unserer Studie, könnte möglicherweise bei Patienten mit Vorhofflimmern zusätzlich zu medikamentöser oder nach invasiver Behandlung wie der Pulmonalvenenisolation das Therapieresultat verbessern und die Rezidivrate verringern.
The regulation of temporo-spatial compartmentalization of protein synthesis is of crucial importance for a variety of physiologic cellular functions. Here, we demonstrate that the cell membrane-anchored disintegrin metalloproteinase ADAM15, upregulated in a variety of aggressively growing tumor cells, in the hyperproliferative synovial membrane of inflamed joints as well as in osteoarthritic chondrocytes, transiently binds to poly(A) binding protein 1 (PABP) in cells undergoing adhesion. The cytoplasmic domain of ADAM15 was shown to selectively interact with the proline-rich linker of PABP. Immunostainings of adhesion-triggered cells demonstrate an ADAM15-dependent recruitment of PABP to cell membrane foci coinciding with ongoing mRNA translation as visualized by the detection of puromycin-terminated polypeptides. Moreover, the increase in cell membrane-associated neosynthesis of puromycylated proteins upon induction of cell adhesion was proven linked to ADAM15 expression in HeLa and ADAM15-transfected chondrocytic cells. Thus, down regulation of ADAM15 by siRNA and/or the use of a cell line transfected with a mutant ADAM15-construct lacking the cytoplasmic tail resulted in a considerable reduction in the amount of cell membrane-associated puromycylated proteins formed during induced cell adhesion.
These results provide first direct evidence for a regulatory role of ADAM15 on mRNA translation at the cell membrane that transiently emerges in response to triggering cell adhesion and might have potential implications under pathologic conditions of matrix remodeling associated with ADAM15 upregulation.
In order to consider the effects of online publishing on the career of researchers, as well as to encourage both its recognition and its improved positioning within the field and beyond, the CETAF Membership organized two workshops during which specific questions about scientific publishing in taxonomy were addressed: authorship citation and Open Access. The present opinion paper is the result of those workshops held on 19 October 2016 in Madrid and on 4 October 2017 in Heraklion. The discussions were aimed at reconciling the requirements of the relevant nomenclatural codes with recommendations for best practices that are adapted to the evolving landscape of e-publishing. By evaluating the different policies of a range of journals regarding authorship citation, we were able to recognise the conflicting and incoherent practices related to the citation of taxon authorships; an issue that is important to clarify for scientific (explicit source), practical (findability of source) and reputational (citation index) reasons. A collective policy on authorship citation also fits into the wider challenge faced by researchers and institutions, whereby interoperability and traceability become key priorities, both for facilitating access to scientific resources and for generating metrics that accurately represent the activities and output of the community. Publications resulting from publicly-funded research should be considered as an essential part of the research process and there has been a strong move towards Open Access, which increases visibility, citability, innovation and impact. Diverse models of Open Access have appeared in scientific publishing but while they each promote free access to the end user, they are not always equitable for the authors and funders of the original research. Herein we formulate recommendations for the relevant research communities and outline the advantages behind adopting a collective strategy towards the issues of authorship citation and Open Access.
The increase in alternative working arrangements has sparked a debate over the positive impact of increased flexibility against the negative impact of decreased financial security. We study the prevalence and determinants of intermediated work in order to document the relative importance of the arguments for and against this recent labor market trend. We link data on individual participation and losses from a Federal Trade Commission settlement with a Multi-Level Marketing firm with detailed county-level information. Participation is greater in middle-income areas and in areas where female labor market non-participation is higher, suggesting that flexibility offers real benefits. However, losses from MLM participation are higher in areas with lower education levels and higher income inequality, suggesting that the downsides of alternative work are particularly high in certain demographics. Our results illustrate that the advantages and disadvantages of alternative work arrangements accrue to different groups.
The influenza vaccination is recommended for all German pregnant women and health care personnel (HCP). We are the first to publish vaccination rates of mothers of hospitalized newborns and HCP in neonatal units. Between September 2016 and March 2017, data were collected in our level-III neonatology department in this descriptive multidisciplinary study, using an anonymous questionnaire. As a result, 513 persons were asked to participate, including 330 parents and 183 HCP. We received an 80.3% (412/513) response rate, 87.3% (288/330), and 67.8% (124/183) from parents and HCP, respectively. Ten percent (16/160) of mothers and 4.7% (6/127) of fathers had been vaccinated in 2016–2017 and 54.4% (87/160) mothers and 52.2% (66/127) fathers ever in their lifetime. In 2016–2017, 51.2% (21/41) of physicians had been vaccinated, 25.5% (14/55) of nurses, and 50.0% (14/28) of other staff members. When comparing those who had more than five influenza vaccinations in their life time, physicians were at 43.9% (18/41) versus nurses at 10.9% (6/55) (p < 0.01), and other HCP at 7.4% (2/27) (p < 0.01). The influenza vaccine uptake rate of 10% in mothers of hospitalized neonates is disappointingly low, resulting in 90% of hospitalized neonates being potentially vulnerable to influenza infection at a time where the risk for influenza-related complication can be severe.
Die Florenliste von Deutschland enthält die akzeptierten Namen der in Deutschland gefundenen Gefäßpflanzen-Sippen, einschließlich Hybriden, Synonyme in der floristischen Literatur (im Aufbau), Verbreitung in den Bundesländern (im Aufbau), Status der Vorkommen, Angabe zur Betonung der wissenschaftlichen Namen, deutsche Namen (im Aufbau) und Zitate der Erstbeschreibungen (im Aufbau). Nicht enthalten sind die nur kultiviert auftretenden Sippen. Die hier dokumentierte Version 10 wurde am 18. August 2018 unter https://www.kp-buttler.de/ veröffentlicht. Sie enthält 62.620 Namen, die sich auf 11.530 akzeptierte Sippen und 51.090 Synonyme verteilen.
The debate on effects of globalization on welfare states is extensive. Often couched in terms of a battle between the compensation and the efficiency thesis, the scholarly literature has provided contradictory arguments and findings. This article contributes to the scholarly debate by exploring in greater detail the micro-level foundations of compensation theory. More specifically, we distinguish between individual policy preferences for compensatory social policies (unemployment insurance) and human capital-focused social investment policies (education) and expect globalization to mainly affect demand for educational investment. A multi-level analysis of ISSP survey data provides empirical support for this hypothesis. This finding provides an important revision and extension of the classical analytical perspective of compensation theory, because it shows that citizens value the social investment function of the welfare state above and beyond simple compensation via social transfers. This might be particularly relevant in today's skill-centered knowledge economies.
Trotz der sorgsam gepflegten Begriffsgeschichte (kaum ein geistes- oder sozialwissenschaftliches Fachwörterbuch ohne entsprechendes Lemma) scheint 'Religion' ein auffällig unkonkreter, im Grunde ungeklärter Begriff, der in Anbetracht dessen in seinem Alltagsverständnis erstaunlich wenig erklärungsbedürftig scheint. Das Problem der Religionswissenschaft, ihren Gegenstand zu bestimmen, - dies soll hier als Indiz für das Problem mit dem Begriff 'Religion' dienen - liegt vielsagenderweise u. a. darin, dass keine Definition in der Lage ist, alles, was man als Religion zu bezeichnen gewohnt ist, gleichzeitig abzudecken und jeder Definitionsversuch als einseitig und letztlich als voreingenommen abgelehnt wurde. Es gab nie und gibt bis heute keine konsensfähige Definition und einige Fachvertreter*innen geben gar zu bedenken, so etwas wie Religion gebe es im Grunde eigentlich gar nicht.
In einem Brief vom 8. Juli 1891 schreibt der junge Hugo von Hofmannsthal an den acht Jahre älteren Richard Beer-Hofmann von seinen Lektüren in Bad Fusch. Darunter findet sich eine ganze Bandbreite internationaler literarischer und philosophischer Werke: von "Gogol" über "Andersen, Immermann, Maupassant" bis hin zu "Schopenhauer". Während die rezeptionsästhetische Aufnahme und Verarbeitung der erstgenannten Autoren bei den Schriftstellern der Wiener Moderne generell eine eher marginale Rolle spielt, ist die frühe Beschäftigung Hofmannsthals mit Schopenhauer freilich keine Einzelerscheinung. Ganz im Gegenteil gehört der Philosoph in der intellektuellen und literarischen Welt des Fin de Siècle zur Allgemeinbildung und ist bereits seit dem literarischen Realismus von vielen Schriftstellern (z.B. Hebbel, Raabe und Fontane) breit rezipiert, zentrale Aspekte seiner Philosophie sind auf vielfältige Weise poetisch produktiv verarbeitet worden.
Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually switch off the shunt function can be used for intraventricular injections of therapeutics in patients suffering from a communicating hydrocephalus caused by leptomeningeal metastases. These shunt devices avoid the risk of injecting therapeutics through the distal leg of the shunt system into the intraperitoneal space, which may cause toxicity. Furthermore, regular intraventricular injections of chemotherapeutics help to maintain sufficient concentrations in the ventricular space. Therefore, ventriculoperitoneal shunts equipped with an on-off valve are a useful tool to reliably inject chemotherapeutics into the ventricles. In order to systematically assess feasibility, safety, and efficacy of this procedure, we performed a retrospective analysis of all patients with leptomeningeal metastases who had received a shunt system at our institution. In total, six adult patients had a ventriculoperitoneal shunt equipped with an on-off valve implanted. Out of these six patients, two patients subsequently received intraventricular injections of chemotherapeutics. The configuration of the valve setting and the intraventricular injections were easily feasible in the setting of a neuro-oncology department. The complication of a shunt leakage occurred in one patient following the first intraventricular injection. No extra-central nervous system (CNS) toxicities were observed. In summary, ventriculoperitoneal shunts with on-off valves are useful tools for reliable intraventricular administration of therapeutics.
Artificial intelligence (AI)1, together with big data, is the driving force behind the ever-accelerating digital revolution. AI has what it takes to call into question our fundamental concepts and processes of political, social, economic etc. order (Macron, 2018; Zuboff, 2018), and the law will not be spared. Therefore, all societal actors (inter alia from politics, the economy, legal practice and academia) must take responsibility for the crucial twin tasks of determining the right, balanced relationship between AI and the law, and even to hybridise them. ...
Background: No observational studies have evaluated the "real-world" effectiveness of dual bronchodilation comprising a long-acting β2-agonist plus a long-acting muscarinic antagonist vs that of triple therapy (long-acting β2-agonist plus long-acting muscarinic antagonist plus inhaled corticosteroid) in COPD.
Materials and methods: DACCORD is a non-interventional, observational clinical study that recruited patients following COPD maintenance therapy initiation or change in maintenance therapy between or within therapeutic class. Given the non-interventional nature of the study, the decision to initiate or change medication had to be made by the patients’ physicians prior to inclusion in DACCORD. We used a matched-pairs analysis to compare disease progression in two patient groups: those receiving dual bronchodilation vs those receiving triple therapy (each group n=1,046).
Results: In two subgroups of patients matched according to a broad range of demographic and disease characteristics, over 1 year, fewer patients receiving dual bronchodilation exacerbated than those receiving triple therapy (15.5% vs 26.6%; P<0.001), with a greater improvement from baseline in COPD Assessment Test total score at 1 year (mean±SD -2.9±5.8 vs -1.4±5.5; P<0.001). When analyzed according to prior therapy, the highest rate of exacerbations was in patients on triple therapy prior to the study who remained on triple therapy. Those changing from mono-bronchodilator to dual bronchodilation had the greatest COPD Assessment Test total score improvement.
Conclusion: In this "real-life" cohort of patients with COPD, most of whom had not exacerbated in the 6 months prior to entry, triple therapy did not seem to improve outcomes compared with dual bronchodilation in terms of either exacerbations or health status. Our analyses clearly demonstrate the potential impact of prior medication on study results, something that should be taken into account when interpreting the results even of controlled clinical trials.
Staatliches Hacking von Computern und Smartphones hat Konjunktur. Durch das Gesetz zur effektiveren und praxistauglicheren Ausgestaltung des Strafverfahrens vom 17. August 2017 (BGBl. I S. 3202) wurden Online-Durchsuchung und Quellen-TKÜ mittels "Staatstrojanern" zu Standardmaßnahmen im strafrechtlichen Ermittlungsverfahren. Die StPO erlaubt seither den Einsatz von Staatstrojanern in mehreren zehntausend Fällen im Jahr: Sie sind nun immer dann zulässig, wenn bisher eine klassische Telekommunikationsüberwachung gem. § 100a Abs. 1 StPO unter Einbindung der jeweiligen Provider (vgl. § 100b StPO a.F.) vorgenommen wurde.
Background: Treatment complexity rises in line with the number of drugs, single doses, and administration methods, thereby threatening patient adherence. Patients with multimorbidity often need flexible, individualised treatment regimens, but alterations during the course of treatment may further increase complexity. The objective of our study was to explore medication changes in older patients with multimorbidity and polypharmacy in general practice.
Methods: We retrospectively analysed data from the cluster-randomised PRIMUM trial (PRIoritisation of MUltimedication in Multimorbidity) conducted in 72 general practices. We developed an algorithm for active pharmaceutical ingredients (API), strength, dosage, and administration method to assess changes in physician-reported medication data during two intervals (baseline to six-months: ∆1; six- to nine-months: ∆2), analysed them descriptively at prescription and patient levels, and checked for intervention effects.
Results: Of 502 patients (median age 72 years, 52% female), 464 completed the study. Changes occurred in 98.6% of patients (changes were 19% more likely in the intervention group): API changes during ∆1 and ∆2 occurred in 414 (82.5%) and 338 (67.3%) of patients, dosage alterations in 372 (74.1%) and 296 (59.2%), and changes in API strength in 158 (31.5%) and 138 (27.5%) respectively. Administration method changed in 79 (16%) of patients in both ∆1 and ∆2. Simvastatin, metformin and aspirin were most frequently subject to alterations.
Conclusion: Medication regimens in older patients with multimorbidity and polypharmacy changed frequently. These are mostly due to discontinuations and dosage alterations, followed by additions and restarts. These findings cast doubt on the effectiveness of cross-sectional assessments of medication and support longitudinal assessments where possible.
Trial registration: 1. Prospective registration: Trial registration number: NCT01171339; Name of registry: ClinicalTrials.gov; Date of registration: July 27, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.
2. Peer reviewed trial registration: Trial registration number: ISRCTN99526053; Name of registry: Controlled Trials; Date of registration: August 31, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.
Im Beitrag wird die Frage des korporativen Gedächtnisses erörtert, wie es sich 1949–1951 in betriebsinternen Zeitschriften als Basis für eine neue korporative Identität der volkseigenen Textilunternehmen gestaltete. Hierbei wird besonders mit den betriebsinternen, von Arbeiter/innen oder den Gewerkschaften verfassten Zeitschriften "Naše pětiletka" (Unser Fünfjahresplan) des Vlnap-Konzerns und "Mosilana píše" (Mosilana schreibt) des Mosilana-Konzerns gearbeitet. Der Schwerpunkt der Untersuchung liegt auf dem Umgang dieser Zeitschriften mit ihrer korporativen Vergangenheit bzw. mit der Vergangenheit der tschechoslowakischen Textilbranche generell. Trotz der schon 1949 dominierenden Ideologisierung des korporativen Gedächtnisses im Sinne des kommunistischen Regimes zeigen sich vor allem in der Auseinandersetzung darüber, welche Art von Kritik in den neuen Konzernen wünschenswert wäre, durchaus auch nicht machtkonforme Kontinuitäten mit der kapitalistischen Ära. Diese verflüchtigen sich jedoch spätestens im Laufe des Jahres 1951.
This scientific article focuses on Ursula Ackrill’s novel ˮZeiden, im Januarˮ and its aim is to examine the specificity of present-day literature of the Transylvanian Saxons. Starting from the methodological considerations of Jan Assmann and Aleida Assmann, the concept of memorial culture will be exemplified and analyzed through relevant scenes of the novel, in close connection with Leontina Philippi’s approach of writing the chronicle of Codlea. Antonescu’s fascist dictatorship, the obligation for Saxon men to serve in the SS troops, the friendly collaboration between Antonescu and Hitler, the collaboration between German and Saxon military, the role of collaborators at that time, the Saxons’ customs and traditions, the portrait of the Jew of Lipscani street, Bucharest society during the rule of Ion Antonescu are just a few aspects of the novel which emphasize the intercultural character of this writing on the basis of communicative and cultural memory.
Besides some well-established forms like autoritär 'authoritarian'; humanitär 'humanitarian'; new coinages ending with -itär can be found in German. These adjectives are closely related to nouns ending with -ität. From an etymological point of view; these formations are morphologically transparent. Not only are the adjectives new; but -itär emerges as a new suffix.
Intestinal graft-versus-host disease (GvHD) is a life-threatening, inflammatory donor T cell-mediated complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the light of the reported efficacy of interleukin-23 (IL-23)-blockade to mitigate syngeneic intestinal inflammation in inflammatory bowel disease patients, targeting IL-23 and thereby interleukin-17a (IL-17a) producing T helper (Th17) cells as the T cell subset assumed to be mostly regulated by IL-23, has emerged as a putatively general concept to harness immune-mediated mucosal inflammation irrespective of the underlying trigger. However, the role of Th17 cells during allo-response driven colitis remains ambiguous due to a series of studies with inconclusive results. Interestingly, we recently identified granulocyte-macrophage colony-stimulating factor (GM-CSF+) T cells to be promoted by interleukin-7 (IL-7) signaling and controlled by the activating protein-1 transcription factor family member basic leucine zipper transcription factor ATF-like (BATF) as critical mediators of intestinal GvHD in mice. Given the dual role of BATF, the contribution of IL-23-mediated signaling within donor T cells and bona fide Th17 cells remains to be delineated from the regulation of GM-CSF+ T cells in the absence of BATF. Here, we found in a complete MHC class I-mismatched model that genetic inactivation of the IL-23 receptor (IL-23R) or the transcription factor retinoic acid-related orphan receptor gamma t (RORγt) within donor T cells similarly ablated Th17 cell formation in vivo but preserved the T cells’ ability to induce intestinal GvHD in a compared to wild-type controls indistinguishable manner. Importantly, RORγt-independent manifestation of intestinal GvHD was completely dependent on BATF-regulated GM-CSF+ T cells as BATF/RORγt double-deficient T cells failed to induce colitis and the antibody-mediated blockage of IL-7/IL-7R interaction and GM-CSF significantly diminished signs of intestinal GvHD elicited by RORγt-deficient donor T cells. Finally, in analogy to our murine studies, colonic RORC expression levels inversely correlated with the presence of GvHD in allo-HSCT patients. Together, this study provides a crucial example of a BATF-dependent, however, IL-23R signaling- and RORγt-, i.e., Th17 fate-independent regulation of a colitogenic T cell population critically impacting the current understanding of intestinal GvHD.
Das Kleine Schneeglöckchen (Galanthus nivalis) zählt zu den klassischen Frühjahrsgeophyten, wobei die Bezeichnung Wintergeophyt an dieser Stelle viel treffender wäre, denn die Art gehört neben dem Winterling (Eranthis hyemalis) bei uns zu den allerersten blühenden Pflanzen im Jahr. Ihre Blüten erscheinen massenhaft zwischen Januar und März, in milden Jahren blühen einzelne Pflanzen auch schon im Dezember. Somit kommt dem Schneeglöckchen nicht nur unter Botanikern eine symbolische Bedeutung zu: Sein Erscheinen versinnbildlicht das allmähliche Erwachen der Natur nach der Winterruhe und den Neubeginn des Pflanzenjahres.