DFG-OA-Publizieren (2012 - 2017)

Permanent URI for this collectionhttps://openscience.ub.uni-mainz.de/handle/20.500.12030/6948

Browse

Recent Submissions

Now showing 1 - 20 of 421
  • ItemZeitschriftenaufsatzOpen Access
    Early Neolithic genomes from the eastern Fertile Crescent
    (2016) Broushaki, Farnaz; Thomas, Mark G.; Link, Vivian; López, Saioa; van Dorp, Lucy; Kirsanow, Karola; Hofmanová, Zuzana; Diekmann, Yoan; Cassidy, Lara M.; Díez-del-Molino, David; Kousathanas, Athanasios; Sell, Christian; Robson, Harry K.; Martiniano, Rui; Blöcher, Jens; Scheu, Amelie; Kreutzer, Susanne; Bollongino, Ruth; Bobo, Dean; Davoudi, Hossein; Munoz, Olivia; Currat, Mathias; Abdi, Kamyar; Biglari, Fereidoun; Craig, Oliver E.; Bradley, Daniel G.; Shennan, Stephen; Veeramah, Krishna R.; Mashkour, Marjan; Wegmann, Daniel; Hellenthal, Garrett; Burger, Joachim
    We sequenced Early Neolithic genomes from the Zagros region of Iran (eastern Fertile Crescent), where some of the earliest evidence for farming is found, and identify a previously uncharacterized population that is neither ancestral to the first European farmers nor has contributed substantially to the ancestry of modern Europeans. These people are estimated to have separated from Early Neolithic farmers in Anatolia some 46,000 to 77,000 years ago and show affinities to modern-day Pakistani and Afghan populations, but particularly to Iranian Zoroastrians. We conclude that multiple, genetically differentiated hunter-gatherer populations adopted farming in southwestern Asia, that components of pre-Neolithic population structure were preserved as farming spread into neighboring regions, and that the Zagros region was the cradle of eastward expansion.
  • ItemZeitschriftenaufsatzOpen Access
  • ItemZeitschriftenaufsatzOpen Access
    Cue combination anisotropies in contour integration : the role of lower spatial frequencies
    (2015) Persike, Malte; Meinhardt, Günter
    The combination of local orientation collinearity and spatial frequency contrast in contour integration was studied in two experiments using a 2AFC contour detection and discrimination task. Target contours were defined by local orientation collinearity, spatial frequency contrast between contour and background elements, or both cues. Experiments differed in the source of spatial frequency contrast by manipulating the spatial frequency of either contour or background elements. Cue summation gains, defined as the performance benefit of double cue conditions over single cue conditions, were evaluated and tested against the predictions derived from probability summation and linear summation. Summation gains were generally stronger than linear summation and tended to increase with the single-cue performance level until limited by ceiling effects. Cue summation was particularly large when contour elements exhibited a lower spatial frequency than background elements, regardless of the absolute spatial frequency ranges. The highly effective integration of lower spatial frequency contours in cluttered surrounds is discussed in the context of recent findings on high-level neural representations of contour integration as well as feature synergy.
  • ItemZeitschriftenaufsatzOpen Access
  • ItemZeitschriftenaufsatzOpen Access
    Novel dengue virus NS2B/NS3 protease inhibitors
    (2015) Wu, Hongmei; Bock, Stefanie; Snitko, Mariya; Berger, Thilo; Weidner, Thomas; Holloway, Steven; Kanitz, Manuel; Diederich, Wibke E.; Steuber, Holger; Walter, Christof; Hofmann, Daniela; Weißbrich, Benedikt; Spannaus, Ralf; Acosta, Eliana G.; Bartenschlager, Ralf; Engels, Bernd; Schirmeister, Tanja; Bodem, Jochen
    Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the in vitro assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC50s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations.
  • ItemZeitschriftenaufsatzOpen Access
    The preview benefit in single-feature and conjunction search : constraints of visual marking
    (2015) Meinhardt, Günter; Persike, Malte
    Previewing distracters enhances the efficiency of visual search. Watson and Humphreys (1997) proposed that the preview benefit rests on visual marking, a mechanism which actively encodes distracter locations at preview and inhibits them afterwards at search. As Watson and Humphreys did, we used a letter–color search task to study constraints of visual marking in conjunction search and near-efficient single-feature search with single-colored and homogeneous distracter letters. Search performance was measured for fixed target and distracter features (block design) and for randomly changed features across trials (random design). In single-feature search there was a full preview benefit for both block and random designs. In conjunction search a full preview benefit was obtained only for the block design; randomly changing target and distracter features disrupted the preview benefit. However, the preview benefit was restored when the distracters were organized in spatially coherent blocks. These findings imply that the temporal segregation of old and new items is sufficient for visual marking in near-efficient single-feature search, while in conjunction search it is not. We propose a supplanting grouping principle for the preview benefit: When the new items add a new color, conjunction search is initialized and attentional resources are withdrawn from the marking mechanism. Visual marking can be restored by a second grouping principle that joins with temporal asynchrony. This principle can be either spatial or feature based. In the case of the latter, repetition priming is necessary to establish joint grouping by color and temporal asynchrony.
  • ItemZeitschriftenaufsatzOpen Access
    Vector light shift averaging in paraffin-coated alkali vapor cells
    (2016) Zhivun, Elena; Wickenbrock, Arne; Sudyka, Julia; Patton, Brian; Pustelny, Szymon; Budker, Dmitry
    Light shifts are an important source of noise and systematics in optically pumped magnetometers. We demonstrate that the long spin-coherence time in paraffin-coated cells leads to spatial averaging of the vector light shift over the entire cell volume. This renders the averaged vector light shift independent, under certain approximations, of the light-intensity distribution within the sensor cell. Importantly, the demonstrated averaging mechanism can be extended to other spatially varying phenomena in anti-relaxation-coated cells with long coherence times.
  • ItemZeitschriftenaufsatzOpen Access
    The Bruton tyrosine kinase inhibitor ibrutinib abrogates triggering receptor on myeloid cells 1-mediated neutrophil activation
    (2017) Stadler, Nicole; Hasibeder, Astrid; Lopez, Pamela Aranda; Teschner, Daniel; Desuki, Alexander; Kriege, Oliver; Weber, Alexander N. R.; Schulz, Christoph; Michel, Christian; Heβ, Georg; Radsak, Markus
  • ItemZeitschriftenaufsatzOpen Access
  • ItemZeitschriftenaufsatzOpen Access
    The genetic prehistory of domesticated cattle from their origin to the spread across Europe
    (2015) Scheu, Amelie; Powell, Adam; Bollongino, Ruth; Vigne, Jean-Denis; Tresset, Anne; Çakırlar, Canan; Benecke, Norbert; Burger, Joachim
    BACKGROUND: Cattle domestication started in the 9(th) millennium BC in Southwest Asia. Domesticated cattle were then introduced into Europe during the Neolithic transition. However, the scarcity of palaeogenetic data from the first European domesticated cattle still inhibits the accurate reconstruction of their early demography. In this study, mitochondrial DNA from 193 ancient and 597 modern domesticated cattle (Bos taurus) from sites across Europe, Western Anatolia and Iran were analysed to provide insight into the Neolithic dispersal process and the role of the local European aurochs population during cattle domestication. RESULTS: Using descriptive summary statistics and serial coalescent simulations paired with approximate Bayesian computation we find: (i) decreasing genetic diversity in a southeast to northwest direction, (ii) strong correlation of genetic and geographical distances, iii) an estimated effective size of the Near Eastern female founder population of 81, iv) that the expansion of cattle from the Near East and Anatolia into Europe does not appear to constitute a significant bottleneck, and that v) there is evidence for gene-flow between the Near Eastern/Anatolian and European cattle populations in the early phases of the European Neolithic, but that it is restricted after 5,000 BCE. CONCLUSIONS: The most plausible scenario to explain these results is a single and regionally restricted domestication process of cattle in the Near East with subsequent migration into Europe during the Neolithic transition without significant maternal interbreeding with the endogenous wild stock. Evidence for gene-flow between cattle populations from Southwestern Asia and Europe during the earlier phases of the European Neolithic points towards intercontinental trade connections between Neolithic farmers.
  • ItemZeitschriftenaufsatzOpen Access
  • ItemZeitschriftenaufsatzOpen Access
  • ItemSammelbandOpen Access
  • ItemZeitschriftenaufsatzOpen Access
    Ceramide profiles of human serum gangliosides GM2 and GD1a exhibit cancer-associated alterations
    (2012) Kirsch, Stephan; Souady, Jamal; Mormann, Michael; Bindila, Laura; Peter-Katalinić, Jasna
  • ItemZeitschriftenaufsatzOpen Access
    A novel in vitro model to study pericytes in the neurovascular unit of the developing cortex
    (2013) Zehendner, Christoph M.; Wedler, Hannah E.; Luhmann, Heiko
    Cortical function is impaired in various disorders of the central nervous system including Alzheimer's disease, autism and schizophrenia. Some of these disorders are speculated to be associated with insults in early brain development. Pericytes have been shown to regulate neurovascular integrity in development, health and disease. Hence, precisely controlled mechanisms must have evolved in evolution to operate pericyte proliferation, repair and cell fate within the neurovascular unit (NVU). It is well established that pericyte deficiency leads to NVU injury resulting in cognitive decline and neuroinflammation in cortical layers. However, little is known about the role of pericytes in pathophysiological processes of the developing cortex. Here we introduce an in vitro model that enables to precisely study pericytes in the immature cortex and show that moderate inflammation and hypoxia result in caspase-3 mediated pericyte loss. Using heterozygous EYFP-NG2 mouse mutants we performed live imaging of pericytes for several days in vitro. In addition we show that pericytes maintain their capacity to proliferate which may allow cell-based therapies like reprogramming of pericytes into induced neuronal cells in the presented approach.
  • ItemZeitschriftenaufsatzOpen Access
    Cytotoxicity of endoperoxides from the Caribbean sponge Plakortis halichondrioides towards sensitive and multidrug-resistant leukemia cells : acids vs. esters activity evaluation
    (2017) Schirmeister, Tanja; Oli, Swarna; Wu, Hongmei; Della Sala, Gerardo; Costantino, Valeria; Seo, Ean-Jeong; Efferth, Thomas
    The 6-epimer of the plakortide H acid (1), along with the endoperoxides plakortide E (2), plakortin (3), and dihydroplakortin (4) have been isolated from a sample of the Caribbean sponge Plakortis halichondrioides. To perform a comparative study on the cytotoxicity towards the drug-sensitive leukemia CCRF-CEM cell line and its multi-drug resistant subline CEM/ADR5000, the acid of plakortin, namely plakortic acid (5), as well as the esters plakortide E methyl ester (6) and 6-epi-plakortide H (7) were synthesized by hydrolysis and Steglich esterification, respectively. The data obtained showed that the acids (1, 2, 5) exhibited potent cytotoxicity towards both cell lines, whereas the esters showed no activity (6, 7) or weaker activity (3, 4) compared to their corresponding acids. Plakortic acid (5) was the most promising derivative with half maximal inhibitory concentration (IC50) values of ca. 0.20 µM for both cell lines.
  • ItemZeitschriftenaufsatzOpen Access
    The role of auditory transient and deviance processing in distraction of task performance : a combined behavioral and event-related brain potential study
    (2013) Berti, Stefan
    Distraction of goal-oriented performance by a sudden change in the auditory environment is an everyday life experience. Different types of changes can be distracting, including a sudden onset of a transient sound and a slight deviation of otherwise regular auditory background stimulation. With regard to deviance detection, it is assumed that slight changes in a continuous sequence of auditory stimuli are detected by a predictive coding mechanisms and it has been demonstrated that this mechanism is capable of distracting ongoing task performance. In contrast, it is open whether transient detection—which does not rely on predictive coding mechanisms—can trigger behavioral distraction, too. In the present study, the effect of rare auditory changes on visual task performance is tested in an auditory-visual cross-modal distraction paradigm. The rare changes are either embedded within a continuous standard stimulation (triggering deviance detection) or are presented within an otherwise silent situation (triggering transient detection). In the event-related brain potentials, deviants elicited the mismatch negativity (MMN) while transients elicited an enhanced N1 component, mirroring pre-attentive change detection in both conditions but on the basis of different neuro-cognitive processes. These sensory components are followed by attention related ERP components including the P3a and the reorienting negativity (RON). This demonstrates that both types of changes trigger switches of attention. Finally, distraction of task performance is observable, too, but the impact of deviants is higher compared to transients. These findings suggest different routes of distraction allowing for the automatic processing of a wide range of potentially relevant changes in the environment as a pre-requisite for adaptive behavior.
  • ItemZeitschriftenaufsatzOpen Access
    Novel concept of CD4-mediated activation of regulatory T cells for the treatment of graft-versus-host disease
    (2017) Schlöder, Janine; Berges, Carsten; Tüttenberg, Andrea; Jonuleit, Helmut
    Allogeneic hematopoietic stem cell transplantation (aHSCT) is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host-disease (GvHD) after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia. Several novel cell-based immunomodulatory strategies for treatment or prevention of GvHD have been developed. Herein, thymus-derived regulatory T cells (tTreg), essential for the maintenance of peripheral immunologic tolerance, are in the focus of investigation. However, due to the limited number of tTreg in the peripheral blood, a complex, time and cost intensive in vitro expansion protocol is necessary for the production of an efficient cellular therapeutic. We demonstrated that activation of tTreg using the CD4-binding HIV-1 protein gp120 leads to a substantially increased suppressor activity of tTreg without the need for additional expansion. Gp120-activated tTreg prevent GvHD development in a preclinical humanized mouse model. In addition, gp120 is not only effective in prevention but also in therapy of GvHD by suppressing all clinical symptoms and improving survival of treated mice. These data indicate that tTreg activation by gp120 is a feasible and potent strategy for significant functional improvement of tTreg as cellular therapeutic for GvHD treatment without the need of complicated, time intensive and expensive in vitro expansion of isolated tTreg.
  • ItemZeitschriftenaufsatzOpen Access
    Inhalation therapy with the synthetic TIP-like peptide AP318 attenuates pulmonary inflammation in a porcine sepsis model
    (2015) Hartmann, Erik; Ziebart, Alexander; Thomas, Rainer; Liu, Tanghua; Schad, Arno; Tews, Martha; Moosmann, Bernd; Kamuf, Jens; Duenges, Bastian; Thal, Serge; David, Matthias
    BACKGROUND: The lectin-like domain of TNF-alpha can be mimicked by synthetic TIP peptides and represents an innovative pharmacologic option to treat edematous respiratory failure. TIP inhalation was shown to reduce pulmonary edema and improve gas exchange. In addition to its edema resolution effect, TIP peptides may exert some anti-inflammatory properties. The present study therefore investigates the influence of the inhaled TIP peptide AP318 on intrapulmonary inflammatory response in a porcine model of systemic sepsis. METHODS: In a randomized-blinded setting lung injury was induced in 18 pigs by lipopolysaccharide-infusion and a second hit with a short period of ventilator-induced lung stress, followed by a six-hour observation period. The animals received either two inhalations with the peptide (AP318, 2x1 mg kg(-1)) or vehicle. Post-mortem pulmonary expression of inflammatory and mechanotransduction markers were determined by real-time polymerase chain reaction (IL-1beta, IL-6, TNF-alpha, COX-2, iNOS, amphiregulin, and tenascin-c). Furthermore, regional histopathological lung injury, edema formation and systemic inflammation were quantified. RESULTS: Despite similar systemic response to lipopolysaccharide infusion in both groups, pulmonary inflammation (IL-6, TNF-alpha, COX-2, tenascin-c) was significantly mitigated by AP318. Furthermore, a Western blot analysis shows a significantly lower of COX-2 protein level. The present sepsis model caused minor lung edema formation and moderate gas exchange impairment. Six hours after onset pathologic scoring showed no improvement, while gas exchange parameters and pulmonary edema formation were similar in the two groups. CONCLUSION: In summary, AP318 significantly attenuated intrapulmonary inflammatory response even without the presence or resolution of severe pulmonary edema in a porcine model of systemic sepsis-associated lung injury. These findings suggest an anti-inflammatory mechanism of the lectin-like domain beyond mere edema reabsorption in endotoxemic lung injury in vivo.
  • ItemZeitschriftenaufsatzOpen Access
    Evaluation of consistency in spheroid invasion assays
    (2016) Cisneros Castillo, Liliana; Oancea, Andrei-Dumitru; Stüllein, Christian; Régnier-Vigouroux, Anne